Signaling protein signature predicts clinical outcome of non-small-cell lung cancer.

BACKGROUND: Non-small-cell lung cancer (NSCLC) is characterized by abnormalities of numerous signaling proteins that play pivotal roles in cancer development and progression. Many of these proteins have been reported to be correlated with clinical outcomes of NSCLC. However, none of them could provide adequate accuracy of prognosis prediction in clinical application. METHODS: A total of 384 resected NSCLC specimens from two hospitals in Beijing (BJ) and Chongqing (CQ) were collected. Using immunohistochemistry (IHC) staining on stored formalin-fixed paraffin-embedded (FFPE) surgical samples, we examined the expression levels of 75 critical proteins on BJ samples. Random forest algorithm (RFA) and support vector machines (SVM) computation were applied to identify protein signatures on 2/3 randomly assigned BJ samples. The identified signatures were tested on the remaining BJ samples, and were further validated with CQ independent cohort. RESULTS: A 6-protein signature for adenocarcinoma (ADC) and a 5-protein signature for squamous cell carcinoma (SCC) were identified from training sets and tested in testing sets. In independent validation with CQ cohort, patients can also be divided into high- and low-risk groups with significantly different median overall survivals by Kaplan-Meier analysis, both in ADC (31 months vs. 87 months, HR 2.81; P <  0.001) and SCC patients (27 months vs. not reached, HR 9.97; P <  0.001). Cox regression analysis showed that both signatures are independent prognostic indicators and outperformed TNM staging (ADC: adjusted HR 3.07 vs. 2.43, SCC: adjusted HR 7.84 vs. 2.24). Particularly, we found that only the ADC patients in high-risk group significantly benefited from adjuvant chemotherapy (P = 0.018). CONCLUSIONS: Both ADC and SCC protein signatures could effectively stratify the prognosis of NSCLC patients, and may support patient selection for adjuvant chemotherapy.

Viral Etiology Relationship between Human Papillomavirus and Human Breast Cancer and Target of Gene Therapy.

OBJECTIVE: To explore the viral etiology of human breast cancer to determine whether there are novel molecular targets for gene therapy of breast cancer and provide evidence for the research of gene therapy and vaccine development for breast cancer. METHODS: PCR was used to screen HPV16 and HPV18 oncogenes E6 and E7 in the SKBR3 cell line and in 76 paraffin embedded breast cancer tissue samples. RNA interference was used to knock down the expression of HPV18 E6 and E7 in SKBR3 cells, then the changes in the expression of cell-cycle related proteins, cell viability, colony formation, metastasis, and cell cycle progression were determined. RESULTS: HPV18 oncogenes E6 and E7 were amplified and sequenced from the SKBR3 cells. Of the patient samples, 6.58% and 23.68% were tested to be positive for HPV18 E6 and HPV18 E7. In the cell culture models, the knockdown of HPV18 E6 and E7 inhibited the proliferation, metastasis, and cell cycle progression of SKBR3 cell. The knockdown also clearly affected the expression levels of cell cycle related proteins. CONCLUSION: HPV was a contributor to virus caused human breast cancer, suggesting that the oncogenes in HPV were potential targets for gene therapy of breast cancer.

[Age correlates with Gleason score in patients with prostate adenocarcinoma].

OBJECTIVE: To investigate the correlation between age and Gleason score (GS) in patients with prostate adenocarcinoma. METHODS: This study included 674 patients with pathologically confirmed prostate adenocarcinoma. We determined the GS, primary grade, and secondary grade of the cases, and compared them among different age groups. RESULTS: The mean age of the patients was (70.22 ± 8.26) yr, ranging from 25 to 96 years, (69.06 ± 8.35) yr in those with GS 6, (70.55 ± 8.16) yr in GS 7, (70.99 ± 6.54) yr in GS 8, (71.56 ± 9.18) yr in GS 9, and (72.79 ± 11.36) in GS 10. The mean GS, primary grade, and secondary grade were 7.08 ± 1.09, 3.54 ± 0.72, and 3.53 ± 0.66, respectively, and the mean GSs in the < 60 yr, 60-69 yr, 70-79 yr, and ≥ 80 yr groups were 6.86 ± 1.10, 6.99 ± 1.10, 7.08 ± 1.04, and 7.38 ± 1.23, respectively. Those with GS 6, 7, and ≥ 8 accounted for 37.7%, 34.3%, and 28.0%, respectively. The patients aged < 60, 60-69, 70-79, and ≥ 80 years constituted 10.5% (71/674), 30.6% (206/674), 47.6% (321/674), and 11.3% (76/674), respectively. The age of the patients was significantly correlated with GS (r2 = 0.013, P = 0.003) and the primary grade (r2 = 0.014, P = 0.002), but not the secondary grade (r2 = 0.005, P = 0.055). CONCLUSION: Of the prostate adenocarcinoma patients, those aged ≥ 70 years form a larger proportion, and those with GS ≥ 7 comprise a higher percentage. The age of the patient is correlated with Gleason score but has a limited value in its prediction.

[Basic features of the ISUP prostate carcinoma Gleason grading system: a preliminary analysis].

OBJECTIVE: To explore the basic features of the prostate carcinoma Gleason grading system of the International Society of Urological Pathology (ISUP). METHODS: We analyzed the means and proportions of the Gleason score (GS), primary grade (PG), secondary grade (SG) and third grade (TG) of 667 cases of prostate carcinoma. RESULTS: The means of GS, PG, SG and TG were 7.06 +/- 1.10, 3.53 +/- 0.66, 3.53 +/- 0.72 and 4.30 +/- 0.96, respectively. The cases with GS 5, 6, 7, 8, 9 and 10 accounted for 0.4% (3/677), 37.2% (252/677), 34.4% (233/677), 13.7% (93/677), 12.0% (81/677) and 2.2% (15/677), respectively; those with GS < or = 6 and > or = 7 constituted 37.7% (255/677) and 62.3% (422/677); those with GS3 + 3, 4 + 3 and 3 + 4 made up 37.2% (252/677), 19.2% (130/677) and 15.2% (103/677); and the TG cases held 10.3% (70/677), including 30.0% (21/70) of grade 3, 10% (7/70) of grade 4 and 60.0% (42/70) of grade 5. CONCLUSION: Our study showed a high proportion of GS, a low proportion of GS < or = 6, and a high proportion of GS > or = 7 in the ISUP prostate carcinoma Gleason grading system. TG of GS needs to be further understood.

Misdiagnosis of synovial sarcoma - cellular myofibroma with SRF-RELA gene fusion: A case report.

BACKGROUND: Cellular myofibroma is a rare subtype of myofibroma that was first described in 2017. Its diagnosis is often challenging because of its relative rarity, lack of known genetic abnormalities, and expression of muscle markers that can be confused with sarcomas that have myogenic differentiation. Currently, scholars have limited knowledge of this disease, and published cases are few. Further accumulation of diagnostic and treatment experiences is required. CASE SUMMARY: A 16-year-old girl experienced left upper limb swelling for 3 years. She sought medical attention at a local hospital 10 months ago, where magnetic resonance imaging revealed a 5-cm soft tissue mass. Needle biopsy performed at a local hospital resulted in the diagnosis of a spindle cell soft tissue sarcoma. The patient was referred to our hospital for limb salvage surgery with endoprosthetic replacement. She was initially diagnosed with a synovial sarcoma. Consequently, clinical management with chemotherapy was continued for the malignant sarcoma. Our pathology department also performed fluorescence in situ hybridization for result validation, which returned negative for SS18 gene breaks, indicating that it was not a synovial sarcoma. Next-generation sequencing was used to identify the SRF-RELA rearrangement. The final pathological diagnosis was a cellular/myofibroblastic neoplasm with an SRF-RELA gene fusion. The patient had initially received two courses of chemotherapy; however, chemotherapy was discontinued after the final diagnosis. CONCLUSION: This case was misdiagnosed because of its rare occurrence, benign biological behavior, and pathological similarity to soft tissue sarcoma.

[Application of endometrial sampling device during the follow-up visit for the conservative treatment of endometrial cancer].

OBJECTIVE: To study the feasibility of endometrial sampling device as a sampling tool during the follow-up visit for endometrial cancer patients undergone conservative treatment. METHODS: Before the hysteroscopy examination, endometrial sampling device was used to take the endometrium specimens 43 times in 19 patients who had been diagnosed as endometrial cancer or atypical hyperplasia, and were undergone conservative treatment during May 2012 to Mar. 2013. All cases accepted vaginal ultrasound screening before every sampling by endometrial sampling device. The histological results were compared with those done by hysteroscopy. RESULTS: The average age of those patients was (30 ± 6) years old. The mean thickness of the endometrium during the treatment was (0.81 ± 0.65) cm. The qualified rate for the sampling was 95% (41/43). Compared with the specimens undergone by hysteroscopy direct sampling, 32 samples got by the endometrial sampling device with thicker endometrium (0.93 ± 0.70) cm had the same histological results, while the other 9 patients with thinner endometrium (0.40 ± 0.14) cm were not (P = 0.031). CONCLUSION: The endometrial sampling device could be used during the follow-up visit for the conservative treatment patients with endometrial cancer or atypical hyperplasia, the vaginal ultrasound screening should be used together to figure out those with thinner endometrium.

Primary ovarian angiosarcoma: Two case reports and review of literature.

BACKGROUND: Angiosarcoma (AS) is a rare and highly aggressive soft tissue disease that most commonly arises in deep soft tissues. There are only a few reported cases of AS involving the ovary and even fewer reports of the underlying molecular abnormalities. Here, we briefly review two cases of primary ovarian AS (oAS) with specific molecular events and immune checkpoints. The clinical features and prognosis of the disease, diagnosis, differential diagnosis, and new treatment approaches are discussed based on a literature review. CASE SUMMARY: Case 1: A 51-year-old female patient was admitted with right lower limb pain for 5 mo, and lower abdominal pain with hematuria for 1 mo. Partial removal of rectus abdominis muscle and fascia, partial hysterectomy, bilateral salpingo-oophorectomy, and inguinal and pelvic lymphadenectomy were performed. Pathology revealed primary oAS. Fluorescence in situ hybridization revealed c-MYC gene amplification. MESNA + ADM + IFO + DTIC (MAID) regimen was administered, but stable disease was achieved. The patient died 1 mo later. Case 2: A 41-year-old female patient presented with fatigue, nausea, decreased appetite, and diffuse abdominal pain. On physical examination, the abdomen was distended and a complex cystic mass was palpable in the right pelvic cavity. Pathology revealed primary oAS. MAID chemotherapy was administered and programmed death ligand 1 (PD-L1) staining was performed on the tumor samples. The patient benefited from anti-PD-1 immunotherapy and is alive without any evidence of disease 27 mo off therapy in follow-up. CONCLUSION: Long-term survival benefit for primary oAS can be achieved by alternative therapeutic strategies using pathological indicators to inform treatment.

[Significance of prognostic evaluation of International Federation of Gynecology and Obstetrics 2009 staging system on stage I endometrioid adenocarcinoma].

OBJECTIVE: To explore the impact of 2009 International Federation of Gynecology and Obstetrics (FIGO) staging system alteration for stage I endometrioid adenocarcinoma on its' prognosis assessing. METHODS: A retrospective study was carried out on 244 cases with endometrial carcinoma admitted in Peking University People's Hospital from Jan.1995 to Feb.2008. RESULTS: (1) All 244 patients were divided into FIGO 2009 Ia group (n = 200) and FIGO 2009 Ib group (n = 44) according to FIGO 2009 staging system, while they were divided into FIGO 1988 Ia group (n = 34), FIGO 1988 Ib group (n = 156) and FIGO 1988 Ic group (n = 29). The others 25 cases were stage IIa (n = 16) and stage IIIa with merely positive abdominal cytology (n = 9) according to FIGO 1988 staging system.(2) The higher percentage of low-grade in FIGO 1988 Ia group than that in FIGO 2009 Ia group (P = 0.003). Compared with FIGO 2009 Ia group, the age of the patients, surgery extent, the percentage of lymph node excision and received chemotherapy and radiotherapy, there were no difference in FIGO 1988 Ia and Ib group, respectively (P > 0.05). There were 5.9% (2/34) and 6.7% (10/150) found relapse among FIGO 1988 Ia group and FIGO 1988 Ib group, and there were 2.9% (1/34) and 2.7% (4/150) for the two groups died of carcinoma. Compared with FIGO 2009 Ia group, there were not significant difference [7.5% (13/200) vs. 3.0% (6/200); P > 0.05]. The 5 years and 10 years progression-free survival (PFS) of FIGO 1988 Ia group and Ib group were (97.0 ± 3.0)%, (90.9 ± 6.5)% and (95.3 ± 2.1)%, (90.2 ± 3.6)%, respectively, in which there were not significant difference compared with that in FIGO 2009 Ia group [(96.1 ± 1.6)%, (89.6 ± 3.2)%; P > 0.05]. The 5 years and 10 years overall survival (OS) in FIGO 1988 Ia group and Ib group were 100%, (93.8 ± 6.0)% and (96.9 ± 1.8)%, (95.2 ± 2.5)%, respectively, in which there were did not significant difference with that in FIGO 2009 Ia group [(97.9 ± 1.2)%, (93.4 ± 2.8)%; P > 0.05].(3) There were not significant difference between FIGO 1988 Ic group and FIGO 2009 Ib group (P > 0.05) for the age of the patients, grade, surgery extent, lymph node excision, the percentage of received chemotherapy and radiotherapy. Between FIGO 1988 Ic group and FIGO 2009 Ib group, there were 3.4% (1/29) and 6.8% (3/44) cases found relapse, respectively. And there were 0 and 2.3% (1/44) cases died of carcinoma in the two groups, in which there were not differ much either (P > 0.05). The 5 years and 10 years PFS in FIGO 1988 Ic group were all 100%, while they were 100% and (90.9 ± 6.2)% in FIGO 2009 Ib group. The 5 years and 10 years OS in FIGO 1988 Ic group were all 100%, but were 100% and (95.0 ± 4.9)% in FIGO 2009 Ib group, in which they all did not significantly differ much (P > 0.05). (4) The patients in FIGO 2009 Ia group were younger than those in FIGO 2009 Ib group (P < 0.01). The percentage of low grade in FIGO 2009 Ia group were higher than that in FIGO 2009 Ib group (P = 0.029). The percentages of received chemotherapy and radiotherapy in FIGO 2009 Ia group were lower than that in FIGO 2009 Ib group remarkably (P < 0.01). But there were not significant difference in the uterine excision extent and the percentage of lymph node excision between the two groups (P > 0.05). There were not significantly differ in the relapse rates and the death rates between the FIGO 2009 Ia group and FIGO 2009 Ib group (P > 0.05). There were also not significant difference in PFS and OS between the two groups (P > 0.05). CONCLUSIONS: There were not significant difference in the prognosis between FIGO 2009 stage Ia and FIGO 1988 stage Ia and Ib. There were also not significant difference in the prognosis between FIGO 2009 stage Ia and FIGO 2009 stage Ib, which may be due to received more chemotherapy and radiotherapy in FIGO 2009 stage Ib patients.

[Post-transplant lymphoproliferative disorder: a clinicopathologic study of 15 cases].

OBJECTIVE: To study the clinical and histopathologic features, diagnosis, pathogenesis and therapy of post-transplant lymphoproliferative disorders (PTLD). METHODS: The clinical and pathologic features of 15 cases of PTLD were retrospectively analyzed by light microscopy, immunohistochemistry and in-situ hybridization, according to the updated 2008 WHO classification of tumors of hematopoietic and lymphoid tissues. RESULTS: Amongst the 15 cases studied, 14 cases had received allogenic hematopoietic stem cell transplantation (AHSCT) and 1 case had received renal transplantation. There were altogether 12 males and 3 females. The male-to-female ratio was 4:1. The mean age was 30.4 years and the median age was 31 years (range from 9 to 60 years). PTLD developed 1.5 to 132 months after transplantation (median 13.0 months). The mean age of the 14 patients with AHSCT was 28.3 years (range from 9 to 45 years) and PTLD developed 1.5 to 19 months after transplantation (mean 4.5 months). Major clinical presentation included fever and lymphadenopathy. Twelve cases involved mainly lymph nodes and the remaining 3 cases involved tonsils, stomach and small intestine, respectively. The histologic types in 4 cases represented early lesions, including plasmacytic hyperplasia (n = 1) and infectious mononucleosis-like PTLD (n = 3). Seven cases were polymorphic PTLD, with 4 cases containing a predominance of large cells. Graft-versus-host disease was also seen in the case of small intestinal involvement. Four cases were monomorphic PTLD, 3 of which were diffuse large B-cell lymphoma, 1 was plasmablastic lymphoma and 1 was a mixture of monomorphic and polymorphic PTLD. Foci of necrosis were seen in 5 cases. The proliferating index of Ki-67 was high. The positive rate of EBV-encoded RNA in AHSCT was 92.9%. The duration of PTLD onset was shorter in EBV-positive cases (range from 1.5 to 7 months) than EBV-negative cases (range from 19 and 132 months). Some cases were treated by reduction of immunosuppression, antiviral agents or anti-CD20 monoclonal antibody Rituximab. The duration of follow-up in 14 patients ranged from 0 to 8 months. Five of the patients died of the disease. CONCLUSIONS: The diagnosis of PTLD relies on morphologic examination and immunohistochemistry. Most of them are of B-cell origin. EBV plays an important role in the pathogenesis of PTLD. The duration of disease onset is shorter in EBV-positive cases. PTLD in AHSCT cases occurs in younger age group, with shorter duration of onset, as compared to solid organ transplantation. The prognosis of PTLD is poor. The modalities of treatment include reduction of immunosuppression, antiviral agents or anti-CD20 monoclonal antibody Rituximab.

[Clinicopathologic study of 40 cases of mediastinal tumours of haematopoietic and lymphoid tissues].

OBJECTIVE: To study clinical and histopathological features, and diagnosis of mediastinal tumours of haematopoietic and lymphoid tissues (MTHL). METHODS: Forty cases of MTHL were analyzed for clinicopathology by microscopy and immunohistochemical staining and in situ hybridization, according to the updated 2008 WHO classification of tumours of haematopoietic and lymphoid tissues. RESULTS: In 40 cases of MTHL, there were 20 males and 20 females. The ratio of male/female was 1:1. The mean age was 31.8 years and median age was 29 years (range, 12 - 70 years).Superior vena cava syndrome was observed in 28 cases. The specimens of 4 cases were obtained by lumpectomy, whereas 36 cases by biopsy (25 cases by thoracoscopy, 1 by core needle aspiration). Twenty cases lay in anterior mediastinum, and 2 in posterior, 1 in superior, 8 in anterior and superior, 2 in posterior and superior, 2 in anterior and middle, 1 in middle and anterior mediastinum.Frozen section were performed in 28 cases, and 17 cases were diagnosed as tumours of haematopoietic and lymphoid tissues (consistency ratio was 60.7%). Twelve cases were classical Hodgkin lymphomas (cHL) (8 were nodular sclerosis subtype, and 3 were mixed cellarity, 1 was lymphocyte-rich subtype), and 10 were primary mediastinal (thymic) large B cell lymphoma (PMBCL), 10 were precursor lymphocyte neoplasm [8 were T lymphoblastic leukemia/lymphomas (T-LBL), 2 were B-LBL], 1 was MALT lymphoma, 1 was composite lymphoma (PMBCL and cHL), 2 were myeloid sarcomas, 4 were gray zone lymphomas (GZL) (3 had morphology reminiscent of cHL, and 1 of DLBCL, all cases were positive for CD20, PAX5, CD30 and CD15).EBER were detected in 11 cases by in situ hybridization, 2 of which were positive (18.2%), and the 2 positive cases were cHL. CONCLUSIONS: MTHLs occur predominantly in adolescents and young adults, mainly present as superior vena cava syndrome and anterior mediasinal masses. cHL, PMBCL, T-LBL were the most common MTHLs.GZLs mainly occur in young adults, those whose morphology reminiscent of cHL, immunohistochemistry reminiscent of PMBCL, and vice versa. Thoracoscopy, frozen section and a suitable panel of antibodies were practical approaches to MTHL.

[Morphologic changes of fallopian tubal epithelium in ovarian serous tumors].

OBJECTIVES: To study the morphologic changes of fallopian tubal epithelium in patients with ovarian serous epithelial tumors and to explore the relationship between the tubal epithelial changes and tumorigenesis of serous ovarian carcinoma. METHODS: The fallopian tubes in 79 cases of high-grade serous ovarian carcinoma, 12 cases of low-grade serous ovarian carcinoma, 16 cases of serous borderline ovarian tumor and 11 cases of non-ovarian benign tumors were serially examined under light microscope. Immunohistochemical study with EnVision method was used to detect the expression of p53 and bcl-2 protein in the fallopian tubal epithelium in all cases. The occurrences of secretory cell outgrowth (SCOUT), p53 signature, serous tubal intraepithelial carcinoma (STIC) and serous invasive carcinoma were analyzed. RESULTS: SCOUT in tubal epithelium was observed in 60.8% (48/79) of the high-grade serous carcinoma group, 4/12 of the low-grade serous carcinoma group, 3/16 of the serous borderline tumor group and 2/11 of the non-ovarian benign tumor group (P = 0.001). P53 signature, STIC and serous invasive carcinoma occurred only in the fallopian tubal epithelium of patients with high-grade serous ovarian carcinoma, with the positive rates being 29.1% (23/79), 15.2% (12/79) and 44.3% (35/79), respectively. Of the 23 cases with p53 signature, 17 cases had solitary lesion and 6 cases involved more than two sites. A total of 33 p53 signature positive foci were found, with 22 foci located at fimbria and 11 at ampulla. Bcl-2 expression was demonstrated in 90.9% of those foci (30/33). Of the 12 patients with STIC, 7 cases were solitary and 5 cases involved more than two sites. A total of 18 STIC foci were found, with 16 foci located at fimbria and 2 at ampulla. All of them were positive for bcl-2. CONCLUSIONS: SCOUT is found in fallopian tubal epithelium in patients with serous ovarian epithelial tumors, especially high-grade serious carcinoma. On the other hand, p53 signature, STIC and invasive serous carcinoma of tubal epithelium are observed only in patients with high-grade serous ovarian carcinoma, with a predilection of fimbrial involvement. Correlation exists between SCOUT, p53 signature, STIC and high-grade serous ovarian carcinomas. Bcl-2 and p53 immunostaining is helpful for demonstrating such lesions.

[Perivascular epithelioid cell tumor of urinary system: a clinicopathologic analysis of 21 cases].

OBJECTIVE: To study the clinicopathologic features and differential diagnosis of perivascular epithelioid cell tumors (PEComas) occurring in the urinary system. METHODS: The clinicopathologic features of 21 cases of PEComa from September 2002 to September 2010 occurring in the urinary system were retrospectively reviewed. Immunohistochemical study for HMB 45, S-100 protein, smooth muscle actin, desmin, Melan A and Ki-67 was carried out. RESULTS: Amongst the 21 cases studied, there were 5 males and 16 females. The age of patients ranged from 16 to 76 years (median = 51.3 years). Twenty cases occurred in the kidney and 1 in the bladder. The predominant histopathologic subtype of renal PEComas was classic type (10/20), followed by epithelioid type (5/20), smooth muscle type (3/20), inflammatory type (1/20) and sclerosing type (1/20). Immunohistochemical study showed that HMB 45 and smooth muscle actin were positive in 95.2% (20/21) and 80.9% (17/21) cases, respectively. Melan A, desmin and S-100 protein were expressed in 71.4% (15/21), 61.9% (13/21) and 33.3% (7/21) cases, respectively. The mean proliferative index was 1.29% (range = 0 to 5%). HMB 45 and Melan A were expressed in all of the 5 cases of epithelioid PEComas, whereas smooth muscle actin and desmin were only expressed in one of them. There was no significant difference between epithelioid PEComas and non-epithelioid PEComas in the expression of HMB 45, Melan A, smooth muscle actin and desmin. Positive staining for HMB 45 and smooth muscle actin was demonstrated in the case of bladder PEComa. CONCLUSIONS: PEComas of the urinary system predominantly affect the kidney. Epithelioid renal PEComas and bladder PEComa are relatively rare and have unique pathologic features. It is necessary to distinguish PEComas from other malignant tumors. Immunohistochemical study for HMB 45, Melan A and smooth muscle actin is helpful for confirmation of diagnosis.

[Expression and promotor methylation of p73 gene in ovarian epithelial tumors].

OBJECTIVE: To investigate the expression and promoter methylation status of p73 gene in ovarian epithelial tumors and their clinicopathological correlations. METHODS: Tissue microarrays (TMA) consisting of 68 ovarian cancers, 37 ovarian borderline tumors and 21 ovarian benign tumors were constructed. p73 expression was detected by immunohistochemistry (EnVision method). Fresh-frozen tissue samples from 13 cases of ovarian carcinomas and 5 cases of borderline tumors were evaluated for the presence of p73 promoter methylation using bisulfite sequencing. RESULTS: Overall, 92.6% (63/68) ovarian carcinomas expressed p73, with a mean value of 32% (percentage of p73 positive cells in the tumor). The mean value of p73 expression rate (40%) in serous carcinoma (26/26) was higher than those of other cancer types (P = 0.006). The mean value of p73 expression rate (40%) in type II ovarian carcinoma was significantly higher than that in type I ovarian carcinoma (24%, P = 0.010). The expression of p73 was not associated with FIGO stage and histological grade (both P > 0.05). The mean values of p73 expression in ovarian borderline tumor (30/37) and benign tumor (12/21) were 16% and 15%, respectively. Of the two groups, the mean value of p73 expression rate in serous type was higher than that in mucous type (P = 0.003, P = 0.026). Ovarian carcinomas had a higher level of p73 expression than borderline tumors and benign tumors (both P < 0.05), while that between ovarian borderline tumors and benign tumors had no statistical difference (P > 0.05). Among serous tumors (49/53), the mean value of p73 expression in the carcinoma group (26/26) was significantly higher than those in the borderline tumor group (12/14) and benign tumor group (11/13; P = 0.024 and P = 0.002, respectively), while that between borderline tumor group and benign tumor group had no statistical difference (P = 0.428). Among mucous tumors (15/27), the mean value of p73 expression in carcinoma group (6/7) was higher than that in benign tumor group (1/8; P = 0.032). No statistical difference of p73 expression was seen between the carcinoma group and ovarian borderline tumor group (8/12) and between the borderline tumor group and benign tumor group (P = 0.234, P = 0.201, respectively). p73 promotor methylation was found in 8 of 13 cases of carcinomas but at different methylation levels with a mean value of 8.0%. Two of 5 ovarian borderline tumors showed detectable p73 promotor methylation with a mean value of 9.0%. Compared with the borderline tumors, ovarian carcinomas showed a similar p73 methylation level (P > 0.05). The p73 methylation level in ovarian carcinomas was not associated with histological type, pathogenetic type, histological grade and FIGO stage (all P > 0.05). CONCLUSIONS: Most of ovarian epithelial tumors express p73 protein with mean values higher in ovarian carcinomas than those in the borderline and benign tumors. Ovarian serous carcinomas have the highest expression level of p73. A simple linear correlation does not exist between the promoter methylation and protein expression of p73.

Neoadjuvant chemotherapy for locally advanced cervical cancer reduces surgical risks and lymph-vascular space involvement.

Neoadjuvant chemotherapy (NACT), which can reduce the size and therefore increase the resectability of tumors, has recently evolved as a treatment for locally advanced cervical cancer. NACT has been reported to decrease the risk of pathologic factors related to prognosis of cervical cancer. To further assess the effects of NACT on surgery and the pathologic characteristics of cervical cancer, we reviewed 110 cases of locally advanced cervical cancer treated with radical hysterectomy with or without NACT at the People's Hospital of Peking University between January 2006 and December 2010. Of 110 patients, 68 underwent platinum-based NACT prior to surgery (NACT group) and 42 underwent primary surgery treatment (PST group). Our results showed 48 of 68 (70.6%) patients achieved a complete response or partial response to NACT. Estimated blood loss, operation time, and number of removed lymph nodes during surgery, as well as complication rates during and after surgery were not significantly different between the NACT group and the PST group. The rates of deep stromal invasion, positive parametria, positive surgical vaginal margins, and lymph node metastasis were not significantly different between the two groups. However, the rate of lymph-vascular space involvement (LVSI) was significantly lower in the NACT group than in the PST group (P = 0.021). In addition, the response rate of NACT was significantly higher in the patients with chemotherapeutic drugs administrated via artery than via vein. Our results suggest that NACT is a safe and effective treatment for locally advanced cervical cancer and significantly decreases the rate of LVSI.

[Clinical characteristics of borderline ovarian tumors and stage I epithelial ovarian cancer: an analysis of 143 cases].

OBJECTIVE: To study the clinical pathological characteristics and high risk factors for borderline ovarian tumor (BOT) and stage I epithelial ovarian cancer (EOC). METHODS: A total of 91 patients with BOT and 52 patients with stage IEOC who were diagnosed and treated in the Department of Gynecology, Peking University People's Hospital from November 2002 to May 2010 were recruited in this study. The patients' clinical characteristics were reviewed respectively and compared between the two groups. RESULTS: The women in BOT group were significantly younger than those in EOC group (41.16 ± 14.95 vs. 50.90 ± 14.37,P<0.01). Compared with women with BOT, women with EOC were more likely to be post-menopausal(42.3% vs. 23.1%,P=0.016) and more with family history of malignant tumors (26.9% vs. 13.2%,P=0.04).There were no significant differences in the size of tumors and the serum level of tumor markers. But the size of solid portion of the tumor of EOC was significantly larger than that of BOT(P<0.01). The extent of the increase of CP2 among the patients with EOC was higher than that among the patients with BOT(256.99 vs. 116.59, P=0.028). There was a statistically significant difference between the two groups in tumors' histopathological type(P<0.01). The serous and mucous tumors were more common in EOC group (90.1%, 82/91). In contrary, endometrioid, clear cells and mixed epithelial cancers were more common in EOC group than serous and mucous cancers (44.2%, 23/52). CONCLUSION: Although the clinical presentation of patients with stage I EOC was similar to that of those with BOT, there were significant differences in the patients' age, post-menopausal or not, family history of malignant tumors, size of solid portion of tumors, extent of the increase of the tumor biomarker, especially of CP2 and tumors histopathological type. These clinicopathological characteristics might be helpful for us to make different diagnosis.

[Relationships between the molecular biomarkers and the clinicopathologic features and prognosis in endometrial carcinoma].

OBJECTIVE: To explore the relationships between the expressions of estrogen receptor (ER), progestin receptor (PR), phosphatase and tension homology deleted on chromosome ten (PTEN), p53, Ki-67 and the clinicopathologic features and prognosis in endometrial carcinoma. METHODS: The data of clinical characteristics, pathological types, histological grades, follow-ups and the expressions of molecular markers detected by immunohistochemistry, and collected from 200 patients with primary endometrial carcinoma, were analyzed. RESULTS: (1) In the cases of endometrial carcinoma, the expression rates of ER, PR, PTEN, p53 were 86.5%, 85.5%, 82.1%, and 49.2%, respectively. The expression level of Ki-67 in the tumor tissues was 46.9% ± 24.7%. (2) A negative correlation was observed between the gravidity and the expression of PR (r=-0.191, P=0.007). On the other hand, age and parturition time were in positive correlation with the expression of p53 (r=0.184, P=0.041; r=0.255, P=0.004). (3) The expression rates of ER, PR and p53 in the endometrioid carcinoma exhibited significant differences comparing with other types (P<0.01). (4) A negative correlation was found between the expression of ER and the FIGO staging (r=-0.176, P=0.013). The positive rate of ER in the cases with Stage I was higher than that in cases with Stage II and above (P=0.015). (5) A negative correlation was found between the histological grade and the expressions of ER and PR (r=-0.217, P=0.002; r= -0.317, P=0.000), however, a positive correlation was detected between the grade with the expressions of p53 and Ki-67 (r=0.327, P=0.000; r=0.465, P=0.000). Compared with the grade 3 tumors, the other grades exhibited significant different expression levels of ER, PR, p53, and Ki-67 (P<0.01). (6) A negative correlation was observed between the depth of myometrial invasion and the positive rate of ER (r=-0.142, P=0.047). There were statistically significant different expression rates of ER and PR between the cases whether the cancer invaded the deep myometrium or not (P<0.05). (7) Multivariate survival analysis showed that patients with PR (+) had longer overall survival than those with PR (-) (P=0.011). CONCLUSION: The immunohistochemical study of endometrium samples obtained from dilatation and curettage of uterine will be beneficial to the understanding of the clinicopathologic features of the endometrial carcinoma before the operation. The value of estimating the prognosis using the expressions of ER, PTEN, p53 and Ki-67 was negative, except for the expression of PR.

[Clinical analysis on the lymph nodes metastasis characters and their relation with the prognosis of the endometrial carcinoma patients].

OBJECTIVE: To explore the lymph nodes (LN) metastasis characters of the endometrial carcinoma and its relation with the patients' prognosis. METHODS: A retrospective study was carried out on 227 cases of endometrial carcinoma who admitted to our department and underwent LN excision from Jul.2000 to Feb.2008. RESULTS: Among 227 cases who underwent pelvic LN excision, there were 22 cases (9.7%) presented LN metastasis. There were 12 cases with positive external iliac LN from 20 cases of patients with data in LN grouping. Para-aortic LN excision was carried out on 138 patients. There were 6 cases with positive para-aortic LN, 5 cases of them together with pelvic LN metastasis. Those patients with cervix involvement, annex metastasis, deep myometrium infiltration, grade 2-3 and negative estrogen receptor occurred pelvic LN metastasis more frequently than the others (P < 0.05). Among the 6 cases with positive para-aortic LN, there were 3 cases (3/6) with deep myometrium infiltration. For those whose para-aortic LN was negative, it was only 16.7% (22 cases). But there were no difference statistically between them (P > 0.05). There were significant difference in 3 years disease-free survival rate between patients with positive pelvic LN or negative pelvic LN [(81.8 ± 8.2)% vs (97.4 ± 1.2)%, P = 0.004]. While there were not significant difference in 3 years disease-free survival rate between patients with positive para-aortic LN or negative para-aortic LN [100% vs (96.7 ± 1.6)%, P > 0.05]. Single factor analysis showed that the age more than 50 years, annex metastasis and pelvic LN metastasis related with the recurrence (P < 0.01). But cervix involvement, deep myometrium infiltration, para-aortic LN metastasis, pathology type, tumor grade and estrogen receptor did not relate with the recurrence (P > 0.05). Cox regression analysis showed that annex metastasis and the age of patients were independent risk factors affecting the recurrence (P = 0.011, P = 0.025). CONCLUSIONS: The most common site of pelvic LN metastasis is the external iliac LN for endometrial carcinoma patients. The patients with positive para-aortic LN always accompanied pelvic LN metastasis. Those patients with cervical involvement, annex metastasis, deep myometrium infiltration, poor differentiation and negative estrogen receptor be more likely exist pelvic LN metastasis. Pelvic LN metastasis may affect the prognosis of endometrial carcinoma patients.

[An analysis on the clinicopathological characteristics of 79 cases atypical endometrial hyperplasia].

OBJECTIVE: To explore the clinicopathological characteristics in atypical endometrial hyperplasia patients. METHODS: A retrospective study was carried out on 79 cases with atypical endometrial hyperplasia patients admitted to Department of Gynecology, Peking University People's Hospital from Mar. 2007 to Jul. 2010. All patients were divided into two groups, hyperplasia group (merely atypical endometrial hyperplasia, 49 cases, 62%) and cancerization group (atypical endometrial hyperplasia accompanying endometrial carcinoma, 30 cases, 38%). RESULTS: The mean age of 79 cases were (50 ± 11) years old, while they were (50 ± 10) and (51 ± 11) years old for hyperplasia group and cancerization group, there were not difference (P = 0.994). The gravidity and delivery frequencies were also not differently between two groups. The rates of complicated other diseases were 47% (23/49) and 43% (13/30), which was not significantly different (P = 0.755). The body mass index (BMI) of cancerization group was higher than that of hyperplasia group [(27.9 ± 5.4) vs. (25.2 ± 2.9) kg/m², P = 0.024]. There were 50% (15/30) and 31% (15/49) menopause cases in two groups, respectively. Among them there were 13/15 and 8/15 cases showed vaginal bleeding. Among premenopausal patients, there were 12/15 and 68% (23/34) showed abnormal vaginal bleeding, but there were not significantly different between two groups (all P > 0.05). The uterine cavity mass found by ultrasonography in the cancerization group patients was more than that in hyperplasia group [73% (22/30) vs. 51% (25/49), P = 0.050]. There were 23 cases (29%), 44 cases (56%) and 12 cases (15%) were diagnosed by dilatation and curettage (D&G), hysteroscopy and hysterectomy, respectively. The rates of diagnosing atypical endometrial hyperplasia by D&G and hysteroscopy were 87% (21/23) and 93% (41/44), respectively. The rate of diagnosis of canceration were 6/12 and 12/16, respectively. While, the rate of missed diagnosis of canceration in the atypical endometrial hyperplasia patients by D&G and hysteroscopy were 6/13 and 19% (4/21), respectively. Which all did not shown significantly different (P > 0.05). CONCLUSION: Hysteroscopy or D&G should be chosen on those peri-menopausal patients with abnormal bleeding, while those atypical endometrial hyperplasia patients with high BMI and uterine cavity mass diagnosed with D&G and ultrasonography should consider the possibility of canceration.

[Immunohistochemistry of p57 and p53 protein in differential diagnosis of hydropic abortion, partial and complete hydatidiform mole].

OBJECTIVE: To investigate the role of p57 and p53 immunohistochemistry in the differential diagnosis of hydropic abortion, partial hydatidiform mole and complete hydatidiform mole. METHODS: Immunohistochemical stains (EnVision method) for p57 and p53 were performed in tissue samples of normal placenta chorionic villi (n=10), abortion chorionic villi (n=12), partial hydatidiform (n=23) and complete hydatidiform moles (n=20). RESULTS: The expression of p57 was predominantly localized in the nuclei of villous cytotrophoblasts and stromal cells. The positive rates of p57 in normal placenta, hydropic abortion and partial hydatidiform mole were 10/10, 12/12, and 100% (23/23), respectively, with no significant difference among the groups (P>0.05). However, none of the complete hydatidiform moles analyzed exhibited p57 positivity in cytotrophoblasts and stromal cells. There was a significant difference between partial and complete hydatidiform moles (P<0.05). The expression of p53 was observed in the nuclei of cytotrophoblastic cells and intermediate trophoblasts. No p53 expression was seen in normal placenta and only 1 of 12 hydropic abortion showed p53 positivity. The positive rates of p53 expression in partial and complete hydatidiform mole were 60.9% (14/23) and 85.0% (17/20) respectively. It was significantly higher in partial hydatidiform mole than that in hydropic abortion. A significant difference was also found between partial and complete hydatidiform moles (P<0.05). CONCLUSIONS: Our findings confirm that p57 immunohistochemistry assists the differential diagnosis of complete hydatidiform mole from partial hydatidiform mole. Expression of p53 may be helpful in distinguishing partial hydatidiform mole from hydropic abortion.

Risk factors evaluation of post-transplant lymphoproliferative disorders after allogeneic haematopoietic stem cell transplantation with comparison between paediatric and adult.

To describe the clincopathological features and evaluate risk factors of post-transplant lymphoproliferative disorder (PTLD) after allogeneic haematopoietic stem cell transplants (allo-HSCT), with comparison between paediatric and adult .Clinicopathological features of 81 cases of PTLD after allo-HSCT were analysed by histopatholgy, immunohistochemistry and in situ hybridisatioin.The cases included 58 males and 23 females with a median age of 26.7 years (range 6-55 years) and the PTLDs developed 1-60 months post-transplant (mean 5.9 months). The histological types indicated 10 cases of non-destructive PTLD, including 4 of plasmacytic hyperplasia, 5 of infectious mononucleosis and 1 of florid follicular hyperplasia. Fifty-six cases were polymorphic PTLD, and 15 were monomorphic PTLD, including thirteen of diffuse large B cell lymphoma, 1 of extranodal nasal type natural killer (NK)/T cell lymphoma and 1 of plasmablastic lymphoma. Foci and sheets of necrosis were observed in 31 cases. The infected ratio of Epstein-Barr virus (EBV) was 91.4%. Some cases were treated by reduction of immunosuppression, antiviral therapy, donor lymphocyte infusion or anti-CD20 monoclonal rituximab. Thirty-three cases died. Compared with that of adult, overall survival of paediatric recipient may be better.The first half year after allo-HSCT is very important for the development of PTLD. Type of PTLD, EBV infection and graft-versus-host disease are risk factors. The prognosis of PTLD is poor, and PTLD after allo-HSCT exhibits some features different from that after solid organ transplantation and some differences existing between adult and paediatric recipients.