Esophageal Histological Precursor Lesions and Subsequent 8.5-Year Cancer Risk in a Population-Based Prospective Study in China.

INTRODUCTION: Data on the associations between esophageal histological lesions and risk of esophageal squamous cell carcinoma (ESCC) in general populations are limited. We aimed to investigate these associations in a large Chinese general population to inform future Chinese ESCC screening guidelines. METHODS: We performed endoscopic screening of 21,111 participants aged 40-69 years from 3 high-risk areas of China in 2005-2009, and followed the cohort through 2016. Cumulative incidence and mortality rates of ESCC were calculated by baseline histological diagnosis, and hazard ratios of ESCC, overall and by age and sex, were assessed using the Cox proportional hazards models. RESULTS: We identified 143 new ESCC cases (0.68%) and 62 ESCC deaths (0.29%) during a median follow-up of 8.5 years. Increasing grades of squamous dysplasia were associated with the increasing risk of ESCC incidence and mortality. The cumulative ESCC incidence rates for severe dysplasia/carcinoma in situ, moderate dysplasia (MD), and mild dysplasia were 15.5%, 4.5%, and 1.4%, respectively. Older individuals (50-69 years) had 3.1 times higher ESCC incidence than younger individuals (40-49 years), and men had 2.4 times higher ESCC incidence than women. DISCUSSION: This study confirmed that increasing grades of squamous dysplasia are associated with increasing risk of ESCC and that severe dysplasia and carcinoma in situ require clinical treatment. This study suggests that in high-risk areas of China, patients with endoscopically worrisome MD should also receive therapy, the first screening can be postponed to 50 years, and endoscopic surveillance intervals for unremarkable MD and mild dysplasia can be lengthened to 3 and 5 years, respectively.

CT diagnosis of pleural and stromal invasion in malignant subpleural pure ground-glass nodules: an exploratory study.

OBJECTIVES: To assess the risk of visceral pleural invasion (VPI) and improve the diagnosis of invasive adenocarcinoma (IA) in pure ground-glass nodules (pGGNs) in contact with pleura, through a comprehensive analysis of the thin-section CT features of subpleural malignant pGGNs. METHODS: CT findings and clinical information of 115 consecutive patients in our hospital between January 2012 and December 2015 who met the following criteria were retrospectively studied: (a) thin-section CT within 1 month before surgery proved pGGN in contact with pleura, and (b) the pGGN was confirmed as malignancy by surgery. Univariate analysis and a multivariate logistic regression analysis were conducted to identify the independent risk factors of IA and VPI. RESULTS: No pleural invasion was observed microscopically in any of the pGGNs. Univariate analysis indicated that tumour shape (p = 0.004), relative density (p = 0.038) and the existence of pleural retraction (p < 0.001) were significantly different between the invasive group and pre- or minimally invasive group. Multivariate logistic regression analysis revealed that pleural retraction (OR, 5.663; p < 0.001), lobulated tumour shape (OR, 4.812; p = 0.016) and tumour relative density greater than 1.60 (OR, 4.449; p = 0.001) were independent risk factors of IA. CONCLUSIONS: Pulmonary adenocarcinoma manifesting as pGGN generally does not invade the pleura. A comprehensive consideration of tumour shape, relative density and tumour-pleural relationship can independently predict IA. KEY POINTS: • This study showed that pGGN-like adenocarcinoma generally does not invade the pleura. • This study suggested that persistent pGGN with pleural retraction, lobulated shape and high relative density (> 1.60) may very likely be invasive adenocarcinoma. • Using "relative density" can reduce confounding of contrast agent and respiratory status in analysis of CT images.

Endoscopy screening effect on stage distributions of esophageal cancer: A cluster randomized cohort study in China.

Efficacy of endoscopic screening for esophageal cancer is not sufficiently definitive and lacks randomized controlled trial evidence. The present study proved short-term screening efficacy through describing and comparing disease stage distributions of intervention and control populations. Villages from Linzhou and Cixian were cluster randomly allocated to the intervention or to the control group and the target population of 52 729 and 43 068 individuals was 40-69 years old, respectively, and the actual enrolled numbers were 18 316 and 21 178, respectively. TNM stage information and study-defined stage information of esophageal cases from 2012 to 2016 were collected. Stage distributions were compared between the intervention and control groups in the total target population, as well as in the subgroup populations in terms of enrolment and before or after intervention. There were a total of 199 and 141 esophageal cancer cases in the intervention and control groups, respectively. For the target population, distributions of TNM stage were borderline significant between the two groups after intervention (P = .093). However, subgroup analysis of the enrolled population during the after-intervention period had statistical significance for both TNM and study-defined stage. Natural TNM stage distributions were approximately 32%, 41%, 24% and 3% for stages I to IV vs 71%, 19%, 7% and 3% in the intervention population. The natural study-defined stage distributions from early, middle to advanced stages were approximately 18%, 49% and 33% vs 59%, 33% and 8%. Early-stage esophageal cancer cases accounted for a higher proportion after endoscopy screening, and the efficacy in the target population depends on the intervention compliance.

[Clinicopathological and prognostic significance of ERα and ERß expression in lung carcinomas: a tissue microarray study].

OBJECTIVE: To detect the expression of ERα and ERß in lung carcinomas and investigate their clinicopathological and prognostic significance by using tissue microarray assay and immunohistochemical staining. METHODS: Six hundred and ninety-eight lung cancer specimens were used in this study, including 651 cases of non-small cell lung carcimomas (NSCLCs) and 47 cases of small cell lung cancers (SCLCs). There were 309 cases of adenocarcimoma and 342 cases of squamous cell carcinoma. The expression of ERα and ERß was analyzed by immunohistochemistry on paraffin-embedded sections. RESULTS: In the normal lung tissues, expression of ERα and ERß was 0% (0/35) and 25.0% (9/36), respectively. In the tumor tissues, ERα was expressed in 209 of 295 AC cases (70.8%), 169 of 330 SCC cases (51.2%) and 9 of 47 SCLC cases (19.1%) (P < 0.001). ERß was expressed in 200 of 297 AC cases (67.3%), 140 of 322 SCC cases (43.5%) and 31 of 47 SCLC cases (66.0%) (P < 0.001). In NSCLC, the expression of ERα and ERß was significantly associated with smoking, stage and lymph node metastasis, also with sex refer to ERß (P < 0.05), but not significantly with age, tumor size and degree of differentiation (P > 0.05). Follow-up was completed in 398 NSCLC cases, and no significant correlation was found between the prognosis and expression of ERα and ERß. CONCLUSIONS: The expression of ERα and ERß has significant difference in lung adenocarcinoma, squamous cell carcinoma and small cell lung cancer. In NSCLC, expression of ERα and ERß is associated with smoking, stage, and lymph node metastasis. The expression of ERß is higher in female than in male NSCLC patients.

[Application value of sentinel node biopsy in early stage oral tongue cancer with clinically negative neck].

OBJECTIVE: To evaluate the liability of sentinel node biopsy in the treatment of early stage oral tongue carcinoma with clinically negative neck. METHODS: Eighteen patients with T1 or T2 oral tongue carcinoma were enrolled in the prospective study. Preoperative lymphoscintigraphy and intra-operative hand-held gamma probe techniques were used to detect the sentinel lymph nodes. The sentinel lymph node biopsies were sent to frozen section pathology and the results were compared with specimen of routine selective neck dissection (I ∼ III or I ∼ IV). The accuracy of cervical metastasis prediction was compared between sentinel node biopsy and tumor thickness. RESULTS: Sentinel lymph nodes were identified in all 18 cases. The numbers of sentinel lymph nodes of level Ib, IIa and III were 6, 22 and 2, respectively. In this series, positive sentinel lymph nodes were revealed in 4 cases, which were also positive in the postoperative routine histology.In other cases, both sentinel lymph nodes and routine histology were negative. Both the sensitivity and specificity were 100%. Sentinel lymph node biopsy obviously improved the specificity of predicting cervical metastasis comparing with the tumor thickness. (100% vs. 36.4%). CONCLUSION: Sentinel node biopsy is effective and reliable in the treatment of early stage oral tongue cancer, and deserves clinical application.

[Expression and clinical significance of BRCA1 in human esophageal squamous cell carcinoma].

OBJECTIVE: To investigate the expression of BRCA1 in esophageal squamous cell carcinoma (ESCC) tissues and evaluate its correlation with clinicopathological features as well as the prognosis of ESCC patients. METHODS: The expression of BRCA1 was detected by immunohistochemistry (IHC) in 201 specimens of T3 stage ESCC tissues and corresponding adjacent normal tissues using tissue microarray. The correlation between BRCA1 expression and clinicopathological features of ESCC was determined by chi-square analysis. The cumulative survival rate was analyzed by Kaplan-Meier method. RESULTS: The positive rate of BRCA1 expression in ESCC tissues was significantly higher than that in adjacent normal tissues [88.6% (178/201) vs. 36.8% (74/201), P < 0.001]. There was a significant correlation between the expression of BRCA1 and lymph node metastasis. In the tumors with positive lymph nodes, strong positive expression of BRCA1 was found in 45.0% (49/109), while only 19.6% (18/92) in tumors without lymph node metastasis, showing a significant difference (P < 0.001). A close relationship was also found between the expression of BRCA1 and gross typing of tumors (P < 0.05). The expression of BRCA1 was not significantly correlated with gender, age, tumor location, differentiation, and tumor thrombus (P > 0.05). The results of Kaplan-Meier analysis indicated that ESCC patients with a higher positive rate of BRCA1 expression have a poorer prognosis (P < 0.05). CONCLUSIONS: The expression of BRCA1 is related to the occurrence and development of esophageal carcinoma. BRCA1 protein may serve as a new potential biomarker in estimating the biological behavior of ESCC.

Efficacy of peripheral blood stem cell transplantation versus conventional chemotherapy on anaplastic large-cell lymphoma:a retrospective study of 64 patients from a single center.

Anaplastic large-cell lymphoma (ALCL) is characterized by frequently presenting adverse factors at diagnosis. Many groups believed aggressive treatment strategies such as autologous stem cell transplantation brought survival benefit for ALCL patients. However, few compared these approaches with conventional chemotherapy to validate their superiority. Here, we report a study comparing the efficacy of peripheral blood stem cell transplantation (PBSCT) and conventional chemotherapy on ALCL. A total of 64 patients with primary systemic ALCL were studied retrospectively. The median follow-up period was 51 months (range, 1-167 months). For 48 patients undergoing conventional chemotherapy only, the 4-year event-free survival (EFS) and overall survival (OS) rates were 70.7% and 88.3%, respectively. Altogether, 16 patients underwent PBSCT, including 11 at first remission (CR1/PR1), 3 at second remission, and 2 with disease progression during first-line chemotherapy. The 4-year EFS and OS rates for patients underwent PBSCT at first remission were 81.8% and 90.9%, respectively. Compared with conventional chemotherapy, PBSCT did not show superiority either in EFS (P = 0.240) or in OS (P = 0.580) when applied at first remission. Univariate analysis showed that patients with B symptoms (P = 0.001), stage III/IV disease (P = 0.008), bulky disease (P = 0.075), negative anaplastic lymphoma kinase (ALK) expression (P = 0.059), and age ≤ 60 years (P = 0.054) had lower EFS. Furthermore, PBSCT significantly improved EFS in patients with B symptoms (100% vs. 50.8%, P = 0.027) or bulky disease (100% vs. 52.8%, P = 0.045) when applied as an up-front strategy. Based on these results, we conclude that, for patients with specific adverse factors such as B symptoms and bulky disease, PBSCT was superior to conventional chemotherapy in terms of EFS.

No long-term survival benefit with sustained-release 5-fluorouracil implants in patients with stages II and III gastric cancer.

BACKGROUND: The prognosis of gastric cancer in an advanced stage remains poor. The exact efficacy of the use of intraoperative sustained-release chemotherapy with 5-fluorouracil (5-FU) in advanced-stage gastric cancer is still unelucidated. AIM: To explore the long-term survival benefit of using sustained-release 5-FU implants in stage II and stage III gastric cancer patients. METHODS: Patients with gastric cancer in a locally advanced stage and who underwent an R0 radical resection between Jan 2014, to Dec 2016, in this single institution were included. Patients with pathological diagnoses other than adenocarcinoma were excluded. All included patients were grouped according to whether intraoperative sustained-release (SR) chemotherapy with 5-FU was used or not (NSR). The primary end-point was 5-year overall survival. Kaplan-Meier method with log-rank test was used to analyze the overall survival of patients and Cox analysis was used to analyze prognosis factors of these patients. RESULTS: In total, there were 563 patients with gastric cancer with locally advanced stage, who underwent an R0 radical resection. 309 patients were included in the final analysis. 219 (70.9%) were men, with an average age of 58.25 years. Furthermore, 56 (18.1%) received neoadjuvant chemotherapy, and 191 (61.8%) were in TNM stage III. In addition, 158 patients received intraoperative sustained-release chemotherapy with 5-FU and were included in the SR group, while the other 161 patients were included in the NSR group. The overall complication rate was 12.94% in the whole group and 10.81%, 16.46% in SR and NSR groups, respectively. There were no significant differences between the two groups in overall survival and complication rate (P > 0.05). The multivariate cox analysis indicated that only N Stage and neoadjuvant therapy were independent influencing factors of survival. CONCLUSION: Intraoperative sustained-release chemotherapy usage with 5-FU, did not improve the survival of patients who underwent an R0 radical resection in locally advanced stage of gastric cancer.

Impact of mature tertiary lymphoid structures on prognosis and therapeutic response of Epstein-Barr virus-associated gastric cancer patients.

Background: Epstein-Barr virus-associated gastric cancer (EBVaGC) exhibits unique histological characteristics within the immune-cell-rich microenvironment, but the role of tertiary lymphoid structure (TLS) in EBVaGC is not yet fully understood. Methods: We retrospectively identified EBVaGC from 8517 consecutive GC cases from the two top cancer centers in China. Furthermore, we evaluated the prognostic value of TLS in 148 EBVaGC patients from our institute and then validated it in an external cohort (76 patients). TLS was quantified and its relationships with overall survival (OS) and therapeutic response were further analyzed. Multiplex immunofluorescence staining and targeted sequencing were used to characterize the composition of TLS and the genomic landscape, respectively. Results: In our study, EBVaGC was observed in 4.3% (190/4436) and 2.6% (109/4081) of GCs in the training and validation cohorts, respectively. TLS was identified in the intratumor (94.6%) and peritumor (77.0%) tissues with lymphoid aggregates, primary and secondary (i.e., mature TLSs) follicles in EBVaGC. Kaplan-Meier analysis showed that mature TLS in intratumoral tissues was associated with a favorable OS in the training and validation cohorts (p < 0.0001; p = 0.0108). Multivariate analyses demonstrated that intratumoral TLS maturation, pTNM, and PD-L1 expression were independent prognostic factors for OS (p < 0.05). Furthermore, the mature TLS was significantly associated with a good response to treatment in EBVaGC patients. Interestingly, the mutation frequency of SMARCA4 was significantly lower in the mature TLS groups. Conclusions: Intratumoral mature TLS was associated with a favorable prognosis and good therapeutic response, suggesting that it is a potential prognostic biomarker and predicts a good therapeutic response in EBVaGC patients.

Pathologic responses and surgical outcomes after neoadjuvant immunochemotherapy versus neoadjuvant chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma.

Background: Currently, the role of immunotherapy in neoadjuvant setting for patients with locally advanced esophageal squamous cell carcinoma (ESCC) is gradually attracting attention. Few studies compared the efficacy of neoadjuvant immunochemotherapy (NICT) and neoadjuvant chemoradiotherapy (NCRT). Our study aimed to compare treatment response and postoperative complications after NICT followed by surgery with that after conventional NCRT in patients with locally advanced ESCC. Methods: Of 468 patients with locally advanced ESCC, 154 received conventional NCRT, whereas 314 received NICT. Treatment response, postoperative complications and mortality between two groups were compared. Pathological response of primary tumor was evaluated using the Mandard tumor regression grade (TRG) scoring system. Pathological complete response (pCR) of metastatic lymph nodes (LNs) was defined as no viable tumor cell within all resected metastatic LNs. According to regression directionality, tumor regression pattern was summarized into four categories: type I, regression toward the lumen; type II, regression toward the invasive front; type III, concentric regression; and type IV, scattered regression. Inverse probability propensity score weighting was performed to minimize the influence of confounding factors. Results: After adjusting for baseline characteristics, the R0 resection rates (90.9% vs. 89.0%, P=0.302) and pCR (ypT0N0) rates (29.8% vs. 34.0%, P=0.167) were comparable between two groups. Patients receiving NCRT showed lower TRG score (P<0.001) and higher major pathological response (MPR) rate (64.7% vs. 53.6%, P=0.001) compared to those receiving NICT. However, NICT brought a higher pCR rate of metastatic LNs than conventional NCRT (53.9% vs. 37.1%, P<0.001). The rates of type I/II/III/IV regression patterns were 44.6%, 6.8%, 11.4% and 37.1% in the NICT group, 16.9%, 8.2%, 18.3% and 56.6% in the NCRT group, indicating a significant difference (P<0.001). Moreover, there were no significant differences in the incidence of total postoperative complications (35.8% vs. 39.9%, P=0.189) and 30-d mortality (0.0% vs. 1.1%, P=0.062). Conclusion: For patients with locally advanced ESCC, NICT showed a R0 resection rate and pCR (ypT0N0) rate comparable to conventional NCRT, without increased incidence of postoperative complications and mortality. Notablely, NICT followed by surgery might bring a promising treatment response of metastatic LNs.

Preoperative Concurrent Chemoradiotherapy Versus Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer: Phase II Randomized Study.

Objective: We evaluated and compared the efficacy and safety of neoadjuvant chemoradiotherapy (NACRT) versus neoadjuvant chemotherapy (NACT) for locally advanced gastric cancer (LAGC) in a single-center randomized phase II trial. Methods: Patients with LAGC were enrolled and received either NACT or NACRT, followed by gastrectomy and adjuvant chemotherapy. The primary endpoint was an R0 resection rate. Results: We enrolled 75 patients: 75.7% (NACT, 28/37 patients) and 76.3% (NACRT, 29/38 patients) underwent surgery; R0 resection rates were 73.0% (27/37) and 73.7% (28/38), respectively. The NACRT group had significantly better major pathological response than the NACT group (37.9% vs 17.9%, p = 0.019). Between-group postoperative complications were not significantly different. The median follow-up was 59.6 months; 5-year overall survival (OS) rate was 50.1% (NACT) and 61.9% (NACRT); neither group reached the median OS; median progression-free survival was 37.3 and 63.4 months, respectively. Conclusions: S-1-based NACRT did not improve the R0 resection rate, although it presented better tumor regression with similar safety to NACT. Trial registration: ClinicalTrial.gov NCT02301481.

Expressions of the γ2 chain of laminin-5 and secreted protein acidic and rich in cysteine in esophageal squamous cell carcinoma and their relation to prognosis.

Previous studies have shown that the expressions of the γ2 chain of laminin-5 and secreted protein acidic and rich in cysteine (SPARC) play important roles in oncogenesis and the development of carcinoma. To assess the expressions of laminin-5 γ2 chain and SPARC in esophageal squamous cell carcinoma (SCC), and to clarify the prognostic significance of the expressions of laminin-5 γ2 chain and SPARC in esophageal SCC, we detected the expressions of laminin-5 γ2 chain and SPARC in cancer tissue and corresponding normal mucosa from 116 patients with advanced (stages II-IV) esophageal SCC using the tissue microarray-based immunohistochemistry and analyzed the correlation of the expressions with clinicopathologic characteristics and survival. We found that in normal esophageal tissues, laminin-5 γ2 chain was expressed in the basement membrane, whereas in esophageal SCC tissues, laminin-5 γ2 chain was expressed in the cytoplasm of carcinoma cells, with a positive rate of 72.4%. SPARC was not detected in normal esophageal mucosa, but was expressed in stromal fibroblasts in 84.6% of esophageal SCC cases and in cancer cells in 7.8% of esophageal SCC cases. There was a significant correlation between laminin-5 γ2 chain and stromal SPARC expression in esophageal SCC (Spearman's rho=0.423, P<0.001). The expressions of both laminin-5 γ2 chain and stromal SPARC were correlated with survival (P=0.032 and P=0.034, respectively). In stage-II esophageal SCC, the expression of laminin-5 γ2 chain was significantly correlated with survival (P=0.023), while the expression of SPARC was not significantly correlated with survival (P=0.154). Patients with elevated levels of laminin-5 γ2 chain and SPARC expressions had a poorer prognosis than did those lacking elevated levels of laminin-5 γ2 chain expression and/or elevated levels of SPARC expression (P=0.001). In stage-II esophageal SCC, patients with elevated levels of laminin-5 γ2 chain and SPARC expressions had a poorer prognosis (P<0.001). These results suggest that laminin-5 γ2 chain and SPARC may play roles in the progression of esophageal SCC and their simultaneous expression is correlated with poorer prognosis, especially in patients with stage-II SCC.

[Primary superficial small cell neuroendocrine carcinoma of esophagus: clinicopathologic and immunohistochemical analysis of 15 cases].

OBJECTIVE: To study the clinicopathologic and immunohistochemical features of primary superficial esophageal small cell neuroendocrine carcinoma (ESCNC). METHODS: The clinical, pathologic and immunohistochemical features were retrospectively analyzed in 15 cases of superficial ESCNC. An immunohistochemical study for chromogranin A, neuron-specific enolase, synaptophysin, CD56, TTF-1, 34ßE12, AE1/AE3, and CK10/13 was performed. RESULTS: Superficial ESCNC accounted for 4.8%(15/312) of all cases of superficial carcinoma of the esophagus encountered during the same period. The median survival time was 19 months and the mean survival time was 23.7 months after diagnosis. The one, two and five-year survival rates were 10/15, 5/15 and 1/15, respectively. The immunophenotypic profile was as follows: neuron-specific enolase (15/15), synaptophysin (15/15), AE1/AE3 (15/15), CD56 (14/15), TTF-1 (9/15), chromogranin A (8/15), 34ßE12 (1/15) and CK10/13 (0/15). CONCLUSIONS: Superficial ESCNC is a rare and aggressive malignant tumor with poor prognosis. Surgical resection coupled with post-operative chemoradiotherapy is the mainstay of treatment. The immunohistochemical study is valuable in pathologic diagnosis and differential diagnosis.

[Comparison of histopathologic changes and expression of biomarkers in breast carcinoma before and after neoadjuvant chemotherapy].

OBJECTIVE: To investigate the relationship between the pathologic responses and histologic type, grade, the expression of ER, PR and HER2 and their changes in breast carcinoma before and after neoadjuvant chemotherapy (NAC). METHODS: Two-hundred and nine cases of breast cancer with NAC were analyzed and clinical, pathologic data were evaluated based on the Miller and Payne ( MP) grading system. The expression of ER, PR and HER2 in the cancers before and after NAC were detected by immunohistochemistry (MaxVision method). SPSS 15.0 software was used to conduct statistical analysis. RESULTS: (1) Pathologic responses to the NAC were graded as MP1 (14 cases), MP2 (35 cases), MP3 (106 cases), MP4 (36 cases) and MP5 (18 cases); (2) The expression of ER in core needle biopsy had related negatively to the pathologic response (chi2 = 33.083, P = 0.001). However, the histologic type, grade, ER and PR status, and HER2 expression in surgically-removed specimens had not related to the pathologic response (P>0.05); (3) After NAC, the pathologic type and grade changed in 6. 8% (9/132) and 34.9% (30/86) of the cases, and the rates of changes in the expression of ER, PR and HER2 were 42.4% (75/177), 55.4% (98/177) and 26.6% (46/173) , respectively. Only the expression of HER2 had significant difference between before and after neoadjuvant chemotherapy (P = 0.049). The changes in other data had no relationship with the pathologic response (P>0.05). CONCLUSIONS: Analysis of core needle biopsy can provide important information to predict the pathologic responses to the NAC. The pathologic appearance, grade, ER, PR and HER2 in breast carcinoma may change after NAC. It is necessary to examine the histologic type, grade and the expression of ER, PR and HER2 after NAC once more.

Survival outcomes and prognostic indicators for gastric cancer patients with positive peritoneal wash cytology but no peritoneal metastasis after radical gastrectomy.

BACKGROUND: Positive peritoneal wash cytology with no peritoneal metastasis (CY1P0) is a special type of distant gastric cancer metastasis, which describes a patient with positive peritoneal lavage cytology, but no definitive peritoneal metastasis, and there are no widely accepted treatment guidelines. We enrolled 48 primary CY1P0 gastric cancer patients treated by radical gastrectomy in this study. Our study illustrated the efficacy of radical gastrectomy for CY1P0 gastric cancer patients, and suggested that the pathological N factor and vascular invasion were significant independent risk factors for overall survival (OS). AIM: To assess the survival of CY1P0 gastric cancer patient post-radical gastrectomy, and to identify factors associated with long-term prognosis. METHODS: Our study included 48 patients with primary CY1P0 gastric cancer who had radical gastrectomies at the Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China between 2013 and 2018. R0 resection was achieved in all 48 patients. Twelve patients received neoadjuvant chemotherapy. Thirty patients received adjuvant chemotherapy and four received adjuvant chemoradiotherapy. OS statistics were available for 48 patients. Follow-up continued through March 2020. Univariate and multivariate analyses were performed using a Cox proportional hazards model to identify prognostic factors. RESULTS: Median OS was 22.0 mo (95% confidence interval: 13.366-30.634 mo) post-surgery. Univariate analyses demonstrated that tumor site (P = 0.021), pathological N factor (P = 0.001), pathological T factor (P = 0.028), vascular invasion (P = 0.046), and the level of CA199 prior to initiating therapy (P = 0.002) were significant risk factors for OS. Multivariate analyses demonstrated that pathological N factor (P = 0.001) and vascular invasion (P = 0.031) were significant independent risk factors for OS. CONCLUSION: This study suggested that radical gastrectomy may be efficient for CY1P0 gastric cancer patient post-radical gastrectomy and the pathological N factor and vascular invasion are significant independent risk factors for OS.

[Expression of fascin and CK14 in different histological types of cancer and its differential diagnostic significance].

OBJECTIVE: To investigate and analyze the expression of fascin and CK14 in multiple histological types of cancer and to explore the potential value of the two proteins as markers in diagnosis and differential diagnosis of various cancer types. METHODS: Tissue microarray containing esophageal squamous cell carcinoma (SCC), lung SCC, larynx SCC, uterine cervical SCC, SCC of external genital organs, lung adenocarcinoma, gastric adenocarcinoma, colorectal adenocarcinoma, heptocellular carcinoma, pancreatic ductal adenocarcinoma, breast infiltrating ductal carcinoma, thyroid papillary carcinoma, uterine endometrioid adenocarcinoma, ovarian serous adenocarcinoma and renal clear cell carcinoma, 30 cases each, as well as corresponding normal controls was constructed. The expression of fascin and CK14 among different types of carcinoma and corresponding normal controls was detected by immunohistochemistry. RESULTS: In normal esophagus, bronchus, larynx, uterine cervix and skin, fascin was mainly expressed in the basal cells or reserve cells, but the expression was diffuse in esophageal SCC, lung SCC, larynx SCC, uterine cervical SCC and SCC of external genital organs, with a positive rate of 90.0%, 90.0%, 96.7%, 78.6% and 89.7%, respectively. In the normal tissue of other organs, except breast and uterine endometrium, fascin was negative. In lung adenocarcinoma, gastric adenocarcinoma, colorectal adenocarcinoma, hepatocellular carcinoma, pancreatic ductal adenocarcinoma, breast infiltrating dutal adenocarcinoma, thyroid papillary carcinoma, uterine endometrioid adenocarcinoma, ovarian serous adenocarcinoma and renal clear cell carcinoma, the positive rates were 38.0%, 23.3%, 14.3%, 10.3%, 73.3%, 13.3%, 6.7%, 60.0%, 66.7% and 10.0%, respectively. The difference between fascin expression in SCC and in other histological types was statistically significant (P < 0.001). CK14 was mainly expressed in the basal cells, reserve cells or myoepithelia of normal tissues. The positive rates of CK14 were 76.7%, 36.7%, 83.3%, 60.7% and 96.3% in esophageal SCC, lung SCC, larynx SCC, uterine cervical SCC and SCC of external genital organs, respectively. It was weak and focal in lung adenocarcinoma, gastric adenocarcinoma, colorectal adenocarcinoma, hepatocellular carcinoma, pancreatic ductal adenocarcinoma, breast infiltrating dutal adenocarcinoma, thyroid papillary carcinoma, uterine endometrioid adenocarcinoma, ovarian serous adenocarcinoma, and renal clear cell carcinoma, with a positive rate of 13.3%, 13.3%, 20.7%, 41.4%, 46.7%, 6.7%, 40.0%, 13.3%, 20.0% and 6.7%, respectively. The difference between CK14 expression in SCC and in other histological types was statistically significant (P < 0.001). The difference between co-expression of fascin/CK14 in SCC and in other histological types was also statistically significant (P < 0.001). CONCLUSION: Fascin and CK14 are highly expressed in SCC, compared with other histological types of carcinoma. Combination of fascin and CK14 should be a valuable marker in diagnosis and differential diagnosis of carcinoma.

[Clinical significance of abnormal expression of Aurora-A in human esophageal squamous cell carcinoma with or without lymph node metastasis].

OBJECTIVE: China has the highest incidence and mortality of esophageal carcinoma in the world, and the esophageal squamous cell carcinoma (ESCC) is the major type. In this study, the authors investigated the expression of Aurora-A in stage T3 esophageal squamous cell carcinomas (ESCC) with positive and negative lymph node metastasis, and analyzed its relationship with prognosis of ESCC patients. METHODS: ESCC tissue arrays including 212 specimens had been constructed. The expression of Aurora-A in both ESCC tissues and adjacent normal tissues was determined by immunohistochemical staining. The correlation between Aurora-A protein levels and lymph node status in ESCC and survival rate were statistically analyzed. RESULTS: The positive expression of Aurora-A was 74.07% (140/189) in tumor tissues and 18.52% (35/189) in adjacent normal tissues, showing a significant difference between them (χ(2) = 105.162, P < 0.05). In tumors with positive lymph nodes, strong positive expression of Aurora-A was found in 42.99% (46/107), while only 7.37% (7/95) in tumors with negative lymph nodes, with a statistically significant difference (χ(2) = 36.132, P < 0.05). The cumulative survival rate of the patients with strong Aurora-A-positive tumors was significantly lower than that in patients with Aurora-A-negative tumors (P = 0.0042, P < 0.05). CONCLUSION: The positive expression of Aurora-A in ESCC tissues is much higher than that in adjacent normal tissues. The expression of Aurora-A is higher in lymph node-positive tumors than in the lymph node-negative ones. There is a significantly longer cumulative survival rate in patients with negative Aurora-A expression than that in patients with strong positive Aurora-A expression.

[Expression of cell cycle related proteins cyclin D1, p53 and p21WAF1/Cip1 in esophageal squamous cell carcinoma].

Dysregulation of cell cycle control, especially G1/S phase transition, is implicated in the pathogenesis of most human cancers, including esophageal squamous cell carcinoma (ESCC). However, the clinicopathological significance of aberrant expression of G1/S phase-related proteins in ESCC remains unclear. In the present study, cyclin D1, p21WAF1/Cip1 and p53 protein expression were examined in 148 ESCC cases using immunohistochemistry combined with tissue microarray. We then analyzed the correlations between their expression and clinicopathological parameters and found that overexpression of p53 was associated with lymph node metastasis (P=0.001). p21WAF1/Cip1 down-regulation was an independent prognostic factor by multivariate analysis (RR=0.418, P<0.001). Further more, array-CGH results revealed that cyclin D1 gene was amplified in 45.4% of ESCC patients. This study confirms that dysregulation of G1/S related genes is common in ESCC and reduced expression of p21WAF1/Cip1 protein can predict shorter overall survival time of patients with ESCC.

[Differences between clinical response and pathologic response of breast cancer after neoadjuvant chemotherapy].

OBJECTIVE: to investigate the pathologic basis of the difference between clinical response and pathologic response of breast carcinoma after neoadjuvant chemotherapy. METHODS: two hundred and nine cases of breast cancer with neoadjuvant therapy were analyzed and clinical data were collected from June, 2005 to December, 2007. All patients had core needle biopsy taken before neoadjuvant chemotherapy and were operated within 4 weeks after neoadjuvant chemotherapy. Clinical examination, X-ray of breast and/or B ultrasonography of primary breast focus were taken before and after neoadjuvant chemotherapy. Clinical responses of breast primary focus were evaluated according to RECIST (response evaluation criteria in solid tumors) version 1.1.Pathologic responses of breast primary focus were evaluated according to Miller and Payne (MP) grading system. SPSS 15.0 software was used to statistical analysis. RESULTS: (1) Clinical responses basing on clinical examination showed complete response, partial response, stable disease and progressive response, in 33, 124, 41 and 11 cases respectively. (2) Eighty-seven cases had X-ray of breast taken before and after neoadjuvant chemotherapy. Clinical response basing on X-ray, showed complete response, partial response and stable disease in 8, 42 and 37 cases respectively. (3) Pathologic responses of breast primary focus were as MP1 (14 cases), MP2 (35 cases), MP3 (106 cases), MP4 (36 cases) and MP5 (18 cases). (4) The clinical response basing on clinical examination were related to the pathologic response (χ(2) = 33.668, P = 0.001); and the clinical response basing on X-ray of breast were also related to the pathologic response (χ(2) = 22.404, P = 0.004). (5) The pathologic basis of the difference between the pathologic response and the clinical response basing on X-ray of breast were: embolism of carcinoma, mucinous carcinoma, intraductal carcinoma with ossifying-type calcification, nodular fibrosis and others. CONCLUSIONS: the clinical response may be related to the pathologic response. The difference between the two may be caused by pathologic changes. Some benign and malignant pathologic changes may contribute to the under-estimation of clinical response over pathologic response; whereas embolism of carcinoma may contribute to the over-estimation of clinical response over pathologic response.

[DNA microarrays-based microRNA expression profiles derived from formalin-fixed paraffin-embedded tissue blocks of squammous cell carcinoma of larynx].

OBJECTIVE: To establish DNA microarrays-based microRNA (miRNA) expression profiles of squamous cell carcinoma of larynx, using archived formalin-fixed paraffin-embedded tissue blocks, and to screen out and identify the differentially expressed miRNAs associated with the biological characteristics of this malignant disease. METHODS: Total RNA was prepared from the formalin-fixed paraffin-embedded tissue blocks. After quality identification and fluorescent labeling, the RNA samples were hybridized with the Agilent human miRNA microarrays which contains 723 probes for human miRNAs. The data was processed with the softwares GeneSpring GX and R-Project. RESULTS: From the formalin-fixed paraffin-embedded tumor blocks collected, 24 RNA samples were obtained with the quality accorded to the requirement of miRNA microarray analysis, and both the hybridization and consequent data processing were accomplished. A total of 319 miRNAs were identified and among them 96 were detected in all the 24 formalin-fixed paraffin-embedded blocks of laryngeal carcinoma; and 5 differentially expressed miRNAs (false discovery rate < 0.05) were found to be associated significantly with the lymphatic metastasis of laryngeal squamous cell carcinoma (P < 0.05), including miR-23a(*), miR-28-5p, miR-15a, miR-16 and miR-425. CONCLUSIONS: Histopathological archives of well-annotated formalin-fixed paraffin-embedded tissue specimens are the valuable resources for miRNA study including to collect RNA samples for miRNA microarray analysis. A panel of differentially expressed miRNAs (miR-23a(*), miR-28-5p, miR-15a, miR-16 and miR-425) derived from the miRNA expression profile may serve as the potential molecular biomarkers for the prediction of metastasis development in laryngeal squamous cell carcinoma.