Analyzing the effects of BRCA1/2 variants on mRNA splicing by minigene assay.

As BRCA1/2 gene sequencing become more extensive, a large number VUS (variants of uncertain significance) emerge rapidly. Verifying the splicing effect is an effective means for VUS reclassification. The Minigene Assay platform was established and its reliability was verified in this article. 47 BRCA1 or BRCA2 variants were selected and performed to validate their effect on mRNA splicing. The results showed that, a total of 16 variants were experimentally proved to have effects on mRNA splicing, among which 14 variants were shown to cause truncated proteins by Sanger sequencing. While the other two variants, BRCA2 c.7976 + 3 A > G and BRCA1 c.5152 + 3_5152 + 4insT was analyzed to cause 57 bp and 26 bp base in-frame deletion, respectively. The remaining 31 variants were not shown to cause mRNA splicing abnormity, including several sites at the edge of exons, which were predicted to affect splicing of mRNA by multiple bioinformatic software. Based on our experimental results, 37 variants were reclassified by ACMG rules. Our study showed that experimental splicing analysis was effectual for variants classification, and multiple functional assay or clinical data were also necessary for comprehensive judgment of variants.

Assessment of deep learning assistance for the pathological diagnosis of gastric cancer.

Previous studies on deep learning (DL) applications in pathology have focused on pathologist-versus-algorithm comparisons. However, DL will not replace the breadth and contextual knowledge of pathologists; rather, only through their combination may the benefits of DL be achieved. A fully crossed multireader multicase study was conducted to evaluate DL assistance with pathologists' diagnosis of gastric cancer. A total of 110 whole-slide images (WSI) (50 malignant and 60 benign) were interpreted by 16 board-certified pathologists with or without DL assistance, with a washout period between sessions. DL-assisted pathologists achieved a higher area under receiver operating characteristic curve (ROC-AUC) (0.911 vs. 0.863, P = 0.003) than unassisted in interpreting the 110 WSIs. Pathologists with DL assistance demonstrated higher sensitivity in detection of gastric cancer than without (90.63% vs. 82.75%, P = 0.010). No significant difference was observed in specificity with or without deep learning assistance (78.23% vs. 79.90%, P = 0.468). The average review time per WSI was shortened with DL assistance than without (22.68 vs. 26.37 second, P = 0.033). Our results demonstrated that DL assistance indeed improved pathologists' accuracy and efficiency in gastric cancer diagnosis and further boosted the acceptance of this new technique.

Significance of interstitial fibrosis and p16 in papillary thyroid carcinoma.

We enrolled 264 patients with papillary thyroid carcinoma (PTC). We performed immunohistochemical detection of p16 and determined the degree of interstitial fibrosis (IF). The expression of p16 was associated with pathological tumor-node-metastasis (pTNM) stage and age (p < 0.05). The cancer-specific survival (CSS) was longer in p16-negative patients (195.73 vs. 181.78 months, p = 0.007). p16 was significantly related to the degree of IF (r = 0.130, p = 0.035). PTC patients with no or mild fibrosis tended to have a larger tumor (p = 0.045). The degree of fibrosis was related to the proportion of papillary structure components (p = 0.025). Univariate and multivariate survival analyses showed that relapse-free survival (RFS) was longer in patients with moderate/severe IF (p < 0.05). In summary, p16 was correlated with prognosis and IF of PTC. Patients with moderate/severe IF tend to have better prognosis in RFS.

Histopathological Diagnosis System for Gastritis Using Deep Learning Algorithm.

Objective To develope a deep learning algorithm for pathological classification of chronic gastritis and assess its performance using whole-slide images (WSIs). Methods We retrospectively collected 1,250 gastric biopsy specimens (1,128 gastritis, 122 normal mucosa) from PLA General Hospital. The deep learning algorithm based on DeepLab v3 (ResNet-50) architecture was trained and validated using 1,008 WSIs and 100 WSIs, respectively. The diagnostic performance of the algorithm was tested on an independent test set of 142 WSIs, with the pathologists' consensus diagnosis as the gold standard. Results The receiver operating characteristic (ROC) curves were generated for chronic superficial gastritis (CSuG), chronic active gastritis (CAcG), and chronic atrophic gastritis (CAtG) in the test set, respectively.The areas under the ROC curves (AUCs) of the algorithm for CSuG, CAcG, and CAtG were 0.882, 0.905 and 0.910, respectively. The sensitivity and specificity of the deep learning algorithm for the classification of CSuG, CAcG, and CAtG were 0.790 and 1.000 (accuracy 0.880), 0.985 and 0.829 (accuracy 0.901), 0.952 and 0.992 (accuracy 0.986), respectively. The overall predicted accuracy for three different types of gastritis was 0.867. By flagging the suspicious regions identified by the algorithm in WSI, a more transparent and interpretable diagnosis can be generated. Conclusion The deep learning algorithm achieved high accuracy for chronic gastritis classification using WSIs. By pre-highlighting the different gastritis regions, it might be used as an auxiliary diagnostic tool to improve the work efficiency of pathologists.

Overexpression of Forkhead box Q1 correlates with poor prognosis in papillary thyroid carcinoma.

OBJECTIVE: Forkhead box Q1 (FOXQ1), a member of the forkhead transcription factor family, plays important parts in cell cycle, apoptosis, metabolism, immunology and tumour genesis. Its expression has been associated with poor clinical prognosis in various tumours. However, the clinical significance of FOXQ1 in papillary thyroid carcinoma (PTC) has not been fully studied. The purpose of this study was to investigate whether FOXQ1 is correlated with poor prognosis in PTC. DESIGN/METHODS: We performed a retrospective study of 136 PTCs. Immunohistochemistry (IHC) was used to examine the expression of FOXQ1 in 136 PTCs and 47 nodular goitre specimens. Rank-sum test, chi-square test, Kaplan-Meier survival analysis, univariate and multivariate Cox analyses were used to investigate the clinical and prognostic significance of FOXQ1 expression in PTC. RESULTS: The comparison of PTC specimens with nodular goitre with papillary hyperplasia specimens revealed an upregulation of FOXQ1 in PTC. Overexpression of FOXQ1 was observed in 63.24% of PTC and correlated with classic variant, tall variant, distant metastasis, AJCC stage and recurrence. FOXQ1-positive expression was associated with shorter disease-free survival: median disease-free survival of FOXQ1-positive patients was 23 months compared with 128 months for FOXQ1-negative patients (Log-rank χ2  = 12.31, P = 0.00045). Additional independent risk factors in this study were multifocality (recurrence-free survival [RFS]: hazard ratio [HR] = 2.391, P < 0.05), extrathyroidal extension (RFS: HR = 3.906, P < 0.05) and positive expression of FOXQ1 (RFS: HR = 6.385, P < 0.01). CONCLUSIONS: Our results indicated that FOXQ1 may be a useful additional biomarker to evaluate the progression of PTC and to predict likely relapse of disease.

Analysis of the status of EGFR, ROS1 and MET genes in non-small cell lung adenocarcinoma.

PURPOSE: To investigate the status and distribution of epidermal growth factor receptor (EGFR), hepatocyte growth factor receptor (MET), and receptor tyrosine kinase (ROS1) genes in patients with non-small cell lung (NSCL) adenocarcinoma. METHODS: The copy number of the MET gene was detected using fluorescence in situ hybridization (FISH). The splice mutation in exon 14 gene was detected by Sanger sequencing. The mutations in EGFR and the fusion of the ROS1 gene were detected using the fluorescence real-time quantitative PCR method (RT-qPCR). RESULTS: The gene mutation frequency of EGFR was 46.51%. There were 7 types of mutations; exon 19 deletions and exon 21 L858R mutations were most frequent. There were 3 cases of double mutations. The MET gene had increased copy numbers in 9.88% of the NSCL adenocarcinoma patients; 3.49% of MET mutations in NSCL adenocarcinoma included 3 intron mutations. The ROS1 gene fusion frequency was 1.74%. CONCLUSION: The NSCL adenocarcinoma patients who were females, did not have a smoking history, and had high grade of differentiation, had higher EGFR mutation rates. Although the MET gene amplification and ROS1 gene fusion in NSCL adenocarcinoma were low-probability events, detection of the gene status of EGFR, ROS1, and MET will facilitate screening more NSCL adenocarcinoma patients who might benefit from targeted therapy.

Human RNA polymerase II associated factor 1 complex promotes tumorigenesis by activating c-MYC transcription in non-small cell lung cancer.

Human RNA polymerase II (RNAPII)-associated factor 1 complex (hPAF1C) plays a crucial role in protein-coding gene transcription. Overexpression of hPAF1C has been implicated in the initiation and progression of various human cancers. However, the molecular pathways involved in tumorigenesis through hPAF1C remain to be elucidated. The current study suggested hPAF1C expression as a prognostic biomarker for early stage non-small cell lung cancer (NSCLC) and patients with low hPAF1C expression levels had significantly better overall survival. Furthermore, the expression of hPAF1C was found to be positively correlated with c-MYC expression in patient tumor samples and in cancer cell lines. Mechanistic studies indicated that hPAF1C could promote lung cancer cell proliferation through regulating c-MYC transcription. These results demonstrated the prognostic value of hPAF1C in early-stage NSCLC and the role of hPAF1C in the transcriptional regulation of c-MYC oncogene during NSCLC tumorigenesis.

Contrast-enhanced ultrasound may distinguish gallbladder adenoma from cholesterol polyps: a prospective case-control study.

PURPOSE: The aim of this study was to find the independent risk factors related with gallbladder (GB) adenoma compared to cholesterol polyp by contrast-enhanced ultrasound (CEUS). MATERIALS AND METHODS: Between January 2010 and September 2014, a total of 122 consecutive patients undergoing cholecystectomy for GB polypoid lesions were enrolled. Before cholecystectomy, each patient underwent conventional US and CEUS examination and all image features were documented. The patients were divided into adenoma group and cholesterol polyp group according to the pathological findings. All the image features between two groups were statistically compared. RESULTS: There were differences in patient age, lesion size, echogenicity, and vascularity of lesion between two groups (P < 0.05). There were differences in stalk width and enhancement intensity between the two groups (P < 0.05). Multiple logistic regression analysis proved that enhancement intensity, stalk of lesion, and vascularity were the independent risk factors related with GB adenoma (P < 0.05). CONCLUSIONS: CEUS could offer useful information to distinguish adenoma from cholesterol polyp. The treatment algorithm for gallbladder polyp lesions would likely benefit from CEUS as a routine imaging investigation, especially in cases where the polyp is larger than 1 cm.

Antitumor activities of ginseng polysaccharide in C57BL/6 mice with Lewis lung carcinoma.

In the present study, we prepared ginseng polysaccharide (GP) and evaluated its antitumor and immunomodulatory activities in C57BL/6 mice bearing with Lewis lung carcinoma (LLC). Administration of GP (50, 100, and 200 mg/kg) could not only significantly inhibit the growth of transplantable LLC tumor in C57BL/6 mice but also remarkably increase relative weight of spleen and thymus, splenocytes proliferation, and the ratio of CD4(+)/CD8(+) T lymphocyte in peripheral blood in LLC-bearing mice. Furthermore, the serum IL-2 and IFN-γ production and NK cytolytic activity were also prompted in LLC-bearing mice in response to GP treatment at three doses. Additionally, GP showed no side effects such as weight loss in body weight and internal organs (lung, liver, kidney, and heart) as well as inactivity during the experiment. Therefore, GP might be conveniently exploited to be good immune-stimulating modifiers and had the potential value for tumor therapy.

[Study on the morphological features, pathologic diagnosis and differential diagnosis of well-differentiated hepatocellular carcinoma].

OBJECTIVE: To analyze the clinicopathologic characteristics of well-differentiated hepatocellular carcinoma (WD-HCC), and to find clues for its pathologic diagnosis and differential diagnosis. METHODS: Seventy-three cases of WD-HCC were studied with clinical data analysis, gross and microscopic examination. RESULTS: Among the 73 cases, the prevalence of HBV (+) and/or HCV (+) was 94.5% (69/73), liver cirrhosis was 80.8% (59/73), increased hepatic cell density was 95.9% (70/73), dilated and irregular hepatic sinus was 89.0% (65/73), prominent trabecularism was 89.0% (65/73), increased cytoplasmic eosinophilia or basophilia was 90.4% (66/73), glandular-like structure was 16.4% (12/73, and fatty degeneration was 42.4% (31/73) . CONCLUSIONS: There are important clinicopathologic features associated with WD-HCC. These features are useful in the differential diagnosis of WD-HCC with dysplastic nodule (DN), focal nodular hyperplasia (FNH) and hepatocellular adenoma.

[Prognostic value of clinical and pathological characteristics in 48 women with pseudomyxoma peritonei].

OBJECTIVE: To investigate the clinic-pathological characteristics and prognosis of 48 female cases with peritoneal pseudomyxoma(PMP). METHODS: The clinicopathologic features and follow-up data of 48 female patients with PMP diagnosed in the General Hospital of People's Liberation Army from Jan.1982 to Dec.2011 were retrospectively reviewed. The relationship between clinic-pathological characteristics and prognosis were analyzed using log-rank test and Cox proportional hazards model. RESULTS: (1) Clinicopathologic features: the mean age of the 48 cases was 58.8 years (range from 24 to 79 years). SYMPTOMS: abdominal distention and abdominal discomfort were the main symptoms. Imaging examinations showed nonspecific abdominal and pelvic lesions in most cases. TREATMENT: all the 48 patients underwent laparotomy and cytoreductive surgery (CRS), in which 15(31%) patients with completeness of the cancer resection (CCR) -1, 24(50%) cases with CCR-2, and CCR-3 in 9(19%) cases. Six (12%) cases were treated by intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin, 20(42%) patients were treated with different options postoperative adjuvant chemotherapy. Pathological types:the cases were histologically classified into 3 subcategories:disseminated peritoneal adenomucinosis (DPAM), peritoneal mucinous carcinomatosis (PMCA), and PMCA with intermediate or discordant features (PMCA-I/D), which were 22(46%) cases, 9 (19%)cases and 17 (35%)cases, respectively. Appendiceal tumors: 44(92%) cases underwent appendectomy, in which 38 cases presented appendiceal tumors (including 20 cases of low-grade appendiceal mucinous adenoma and 18 cases of appendiceal mucinous adenocarcinoma), 2 cases were diagnosed as appendicitis, 4 cases with unknown pathologic diagnosis. And the other 4(8%) cases, who didn't undergo appendectomy at the first operation, presented peritoneal tumor recurrence and appendiceal mucinous tumors 1, 11, 32 and 85 months after surgery, respectively. Parenchymal organs involved: ovarian involving was happened in 34 (71%) patients including 15 cases with the right ovary involving, 13 cases in both sides, and 6 cases involving the left side. The other parenchymal organs in 10(21%) cases. (2) Prognostic factors: 11 patients died, 31 survived and 6 cases were lost to follow-up. The mean survival time was 99 months(ranged from 1 to 312 months). The 3-year, 5-year and 10-year survival rates were 73.3%, 68.0% and 46.6%, respectively. Univariate statistical analysis showed that age, pathological type and parenchymal involvement were significantly relationship with the survival time (all P < 0.05). But the operation times, appendiceal tumor type, ovarian involvement, CCR, intraperitoneal HIPEC and post-operative adjuvant chemotherapy were not significantly correlate with survival time (all P > 0.05). Multivariate analysis showed that age and pathologic type were independent prognostic factors(P < 0.05). CONCLUSIONS: No specific clinical features presented in PMP. CRS with HIPEC should the recommended treatment. Both ovaries exploration and appendectomy should be carried out routinely in CRS. The 10-year overall survival of PMP is low. Age, pathological type and parenchymal organs involvement other than ovarian are correlated with the prognosis. And the pathological type and age are independent prognostic factors of PMP.

The value of Korean, American, and Chinese ultrasound risk stratification systems combined with BRAF(V600E) mutation for detecting papillary thyroid carcinoma in cytologically indeterminate thyroid nodules.

PURPOSE: To investigate the value of Korean, American, and Chinese ultrasound risk stratification systems combined with BRAF(V600E) mutation in the detection of papillary thyroid carcinoma (PTC)within cytologically indeterminate thyroid nodules (CITNs). METHODS: A single-center retrospective study encompassed 511 CITNs selected from 509 patients between January 2020 and July 2023.Each nodule underwent surgical treatment and was classified according to three distinct systems. Receiver operating characteristic (ROC) curves were plotted using histopathological diagnosis as the reference standard, and diagnostic performance was compared. RESULTS: The three ultrasound stratification systems showed an elevated malignant risk with increasing grades (all P for trend2 < 0.001). The cut-off values for Korean, American, and Chinese systems were 5, 5, and 4c, and their respective area under the curves (AUCs) were 0.735, 0.778, and 0.783.The combination of BRAF (V600E) mutation significantly enhanced the diagnostic efficacy for the Korean(0.773vs0.735, P < 0.001), American (0.809vs0.778, P < 0.001) and Chinese (0.815vs0.783, P < 0.001) stratification systems in distinguishing CITNs without compromising specificity. When the three stratification systems were applied individually or combined with BRAF (V600E) mutation, the AUCs of the American and Chinese systems were similar (all P > 0.05), both of which were higher than the AUC of the Korean system (all P < 0.05). The American system exhibited higher specificity compared to the Chinese and Korean systems (all P < 0.001), whereas the Chinese system demonstrated higher sensitivity and accuracy when compared to the American and Korean systems (all P < 0.001). CONCLUSION: Korean, American and Chinese stratification systems present potential in the differential diagnosis of CITNs. BRAF (V600E) mutation can significantly improve the detection rate of malignant nodules within CTNs, particularly PTC. Notably, the American and Chinese systems demonstrate superior overall diagnostic performance among these systems.

The contribution of strain patterns in characterization of prostate peripheral zone lesions at transrectal ultrasonography.

BACKGROUND: Elasticity is an important characteristic of tissue. During an elastography examination, various strain images of lesions are observed, and a suitable classification of strain patterns (SP) may provide vital diagnostic information about lesions. Numerous studies have shown that ultrasound elastography can improve the detection of prostate cancer, but the diagnostic value of SP classification has not yet been fully evaluated. PURPOSE: To investigate the contribution of SP on the characterization of prostate peripheral zone lesions by transrectal real-time tissue elastography (TRTE) in combination with conventional transrectal ultrasonography (TRUS). MATERIAL AND METHODS: One hundred and seventy-one patients with suspected prostate cancer underwent TRUS and TRTE examinations. The SPs of the suspicious lesions were classified into five scores by TRTE according to the degree and distribution of strain. All findings were confirmed by transrectal systematic 12-core biopsies and targeted biopsies for suspicious areas detecting by TRUS and/or TRTE. RESULTS: One hundred and forty-eight of 171 patients had high-quality TRTE imaging and were included into the study. When a cut-off point of SP score III was used, the area under the receiver-operating characteristic curve (AUC) was, respectively, 0.75 (95% CI: 0.67-0.83), 0.85 (95% CI: 0.78-0.91) and 0.84 (95% CI: 0.77-0.91) for the diagnosis of prostate cancer by TRUS, TRTE and TRTE + TRUS. A linear tendency of SP and Gleason scores was observed in scores III-V. The detection rate of prostate cancer using TRTE-targeted biopsy (75.8%) was significantly higher than that of systematic 12-core biopsy plus TRUS-targeted biopsy (14.5%) (P = 0.00). CONCLUSION: This study suggests the significant contribution of SP on characterization of prostate peripheral zone lesions and the improvement of TRTE-targeted biopsy on detection of prostate cancer.

[Clinicopathologic features of primary thymic extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type].

OBJECTIVE: To study the clinicopathologic features of primary thymic extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT). METHODS: The clinical and pathologic findings were evaluated in 3 cases of biopsy confirmed thymic MALT lymphoma. The clincopathologic features, treatment and prognosis were discussed and literatures reviewed. RESULTS: One male and two female patients presented with asymptomatic mediastinal masses with a history of Sjögren syndrome. They were aged 36, 35 and 41 years respectively, and only one patient had B symptoms. Grossly, all three tumors were encapsulated and had multiple variable-sized cysts on cut-surface. Histopathologically, the normal thymic lobular architecture was effaced by abnormal dense lymphoid infiltration. Prominent lymphoepithelial lesions were formed by centrocyte-like cells infiltrating and expanding Hassall's corpuscles and epithelial cyst lining. All cases showed apparent plasmacytic differentiation. Immunohistochemically, the tumor cells were positive for CD20, CD79a, bcl-2 and negative for CD3, CD5, cyclin D1, CD43, CD10, bcl-6, and CD23. The plasma cells showed kappa light chain restriction. Immunoglobulin heavy chain rearrangement in three cases was confirmed by PCR. All patients were at early stage and received routine chemotherapy with or without radiotherapy after surgical removal. All patients achieved complete remission with 24, 18 and 3 months follow-up, respectively. CONCLUSIONS: Primary thymic MALT lymphoma may be a rare distinctive lymphoma. It can be diagnosed by HE and immunohistochemical study and should be differentiated from reactive lymphoid proliferation, other types of lymphoma and mediastinal thymoma.

[Granulocytic sarcoma: a clinical and pathologic analysis of ten cases].

OBJECTIVE: To investigate the clinical and pathological features, differential diagnosis of granulocytic sarcoma. METHODS: The clinical manifestations, histopathological features, immunohistochemistry, treatment and prognosis were analyzed retrospectively in 10 cases of granulocytic sarcoma. RESULTS: The age of patients ranged from 10 to 56 years (means = 35.8 years). The male-to-female ratio was 1.5:1. Histologically, the malignant cells of granulocytic sarcoma grew in a diffuse pattern. The cytoplasm was scanty, with eosinophilic fine granularity in some cells. The nuclei were round or focally irregular, and had finely dispersed chromatin. The mitotic figures were visible. Immunohistochemical stains for MPO, CD43, CD117, CD34 and CD99 were positive. CONCLUSIONS: Granulocytic sarcoma can occur in patients of all ages with a male predominance. The diagnosis of granulocytic sarcoma is assisted by the cytochemical stain for naphthol-ASD-chloroacetate esterase and/or immunophenotypic analyses for MPO, CD43, CD117, CD34, CD99. These stains aid in the distinction of granulocytic sarcoma from: lymphoblastic lymphoma, Burkitt lymphoma, diffuse large B-cell lymphoma, small round cell tumours, particularly in children, and blastic plasmacytoid dendritic cell neoplasm.

[Clinical and pathologic features of gastric schwannoma].

OBJECTIVE: To study the clinical and pathologic features of gastric schwannomas. METHODS: The macroscopic and microscopic features of 9 cases of gastric schwannoma were analyzed. Immunohistochemical study for S-100 protein, CD117, CD34, neurofilament, desmin, nestin, glial fibrillary acidic protein, platelet derived growth factor-alpha (PDGFR-α) and vimentin was carried out. Mutation analysis of c-kit gene (exon 9, 11, 13 and 17) and PDGFR-α gene (exon 12 and 18) in 1 case was examined by PCR amplification and direct sequencing. RESULTS: The patients included 5 males and 4 females. The age of patients ranged from 42 to 81 years (median = 56.5 years). The size of the tumors ranged from 2 to 9 cm in greatest diameter. Follow-up data in 8 cases (from 1 month to 65 months) showed no evidence of recurrence or metastasis. Gross examination showed that gastric schwannomas were homogeneous, firm, yellow-white and bore no true fibrous capsule. Histologically, all cases were composed of fascicles of spindle cells associated with nuclear palisading, Verocay body formation and peripheral cuff of reactive lymphoid aggregates. Some of them showed degenerative changes including cyst formation, calcification, hemorrhage, necrosis and hyalinization. Immunohistochemical study showed that the tumor cells were strongly positive for S-100 protein and vimentin. There was various degree of staining for nestin (8/9) and glial fibrillary acidic protein (6/9). They were negative for CD117, CD34, neurofilament, desmin and smooth muscle actin. One case showed focal positivity for PDGFR-α (1/9), with no mutations found. CONCLUSIONS: Gastric schwannomas share similar histologic features with conventional soft tissue schwannomas, in addition to the presence a reactive lymphoid cuff. The clinical, macroscopic, histologic and immunohistochemical features of gastric schwannomas were different from those of gastrointestinal stromal tumors and leiomyomas.

[Expression of glypican-3, hepatocyte antigen, alpha-fetoprotein, CD34 and CD10 in hepatocellular carcinoma: a clinicopathologic analysis of 375 cases].

OBJECTIVE: To explore prognostic factors and the expression of glypican-3, hepatocyte antigen (HEP), alpha-fetoprotein (AFP), CD34 and CD10 in hepatocellular carcinoma (HCC) and their prognostic value. METHODS: Clinicopathologic data were analyzed in 375 cases of HCC, in which 80 cases with follow-up were examined by immunohistochemical staining to detect the expression of glypican-3, HEP, AFP, CD34 and CD10 proteins. The relationship between the proteins expression and clinicopathologic features was also evaluated. RESULTS: Tumor number (P = 0.000), tumor size (P = 0.025), tumor differentiation (P = 0.001) and vessel invasion (P = 0.000) were closely related to prognosis of HCC patients; the expression of glypican-3 (66/80,82.5%; P = 0.002), HEP (64/80,80.0%; P = 0.021), AFP (38/80,47.5%; P = 0.014) and CD10 (28/80,35.0%; P = 0.002) was significantly related to tumor differentiation; that of glypican-3 was significantly correlated with tumor number and presence of satellite nodules (P = 0.028) and that of AFP and CD10 was significantly correlated with portal vein thrombi (P = 0.000, P = 0.010). On Kaplan-Meier regression analysis, both low expression of HEP and high expression of AFP were closely related to poor prognosis. CONCLUSIONS: Tumor number, size, differentiation and vessel invasion were important factors affecting the prognosis of patients with HCC. HEP and AFP have prognostic significance in HCC.

[Expression of granulocyte colony stimulating factor in patients with non-small cell lung cancer and its clinicopathological significance].

OBJECTIVE: To examine granulocyte colony stimulating factor (G-CSF) expression in human non-small cell lung cancer (NSCLC) as well as discuss its clinicopathological significance. METHODS: Specimens were obtained from 114 cases (53 cases with granulocyte infiltration) diagnosed pathologically as NSCLC in General Hospital of PLA. Paraffin-embedded tissues from these 114 cases of NSCLC were examined for expression of G-CSF by immunohistochemical staining. Correlation between G-CSF expression and pathological features, clinical manifestation, prognosis of patients with NSCLC was analyzed statistically. All the patients were retrospectively followed-up. RESULTS: Fifty-five of the 114 NSCLC specimens expressed G-CSF, and among these 41 (41/54, 75.9%) were large cell carcinoma, nine (9/30, 30.0%) were adenocarcinoma and five (5/30, 16.7%) were squamous cell carcinoma. The expression was significantly correlated with infiltration of tumor mass by neutrophilic granulocytes, histological type, necrosis, differentiation, lymph node metastases, distant metastases, recurrence and survival period (P < 0.01). There was no significant correlation with primary tumor size (P > 0.05). Logistic multi-factor analysis revealed that necrosis, lymph nodes metastases and distant metastases RR (risk ratio) in G-CSF positive group was 5.57, 6.28 and 5.24 times higher than those of G-CSF negative group (P < 0.05). There were remarkable difference of 5-year survival rates (0 and 12.1% respectively) and survival period (42 and 62 months respectively) between positive and negative groups (P < 0.01). CONCLUSIONS: NSCLC with G-CSF excretion are mainly large cell lung cancer. The pathologic characteristics of these cases with G-CSF expression included poor differentiation, remarkable atypia, prominent necrosis and infiltration of tumor mass by neutrophils or emperipolesis. These tumors are usually more aggressive in biological behavior and have worse prognosis than those without G-CSF expression.

Clinicopathological features of sclerosing angiomatoid nodular transformation of the spleen.

PURPOSE: To explore the clinicopathological features of sclerosing angiomatoid nodular transformation (SANT) of the spleen. METHODS: The clinicopathological data of 26 SANT patients were analyzed. RESULT: There were 15 men and 11 women, aged 23-62 years (mean: 43.9 years; median: 43 years). Twenty patients were found during health check-ups. Magnetic resonance imaging had significantly higher specificity than other imaging modes in the diagnosis of SANT. Macroscopically, the lesions were gray-red and gray-white, along with well-demarcated nodules. Microscopy showed multiple angiomatoid nodules embedded in hyperplastic fibrous tissues and dense collagen fiber; the angiomatoid structures inside the nodules had varied morphology. Patchy and nodular fresh and old hemorrhages were observed in each lesion. Proliferative fibroblasts were seen in the stroma, along with infiltration of a few mixed inflammatory cells. Serum tumor markers were negative. Fourteen patients (53.8 %) had benign or malignant lesions in other parts of the body, including the liver, kidneys, and adrenal and pituitary glands which were similar to von Hippel-Lindau (VHL) syndrome. The reasons for occurrence of SANT may be as follows: hemangioma/lymphangioma or splenic congestion with extensive hemorrhage and secondary changes. CONCLUSIONS: SANT is a rare benign vascular lesion with some clinical manifestations similar to VHL syndrome. Patients have good prognosis after tumor removal.

CT and MRI features of sclerosing angiomatoid nodular transformation of the spleen: A report of 18 patients with pathologic correlation.

PURPOSE: The purpose of this study was to describe the computed tomography (CT) and magnetic resonance imaging (MRI) features of sclerosing angiomatoid nodular transformation (SANT) of the spleen and correlate imaging features with those obtained at histopathologic analysis. MATERIALS AND METHODS: A total of 18 patients (9 men, 9 women; mean age, 42.2±10.7 [standard deviation (SD)] years; range, 23-59 years) with histopathologically confirmed SANT were retrospectively evaluated. The presenting symptoms, gross pathologic changes, and histopathologic and correlative immunohistochemical results were recorded. CT (n=8) and MRI (n=12) features were analyzed by two radiologists and included number, size, shape, boundary, attenuation, signal intensity, and enhancement patterns. RESULTS: Seventeen patients (17/18; 94%) had a single SANT without specific clinical symptoms and one patient (1/18; 6%) had multiple SANTs with left-upper-quadrant bloating and pain. The largest lesion diameter exceeded 3cm. On plain CT images, SANTs were slightly hypoattenuating in seven patients (7/8; 88%), isoattenuating in one patient (1/8; 13%), and contained calcification in two patients (2/8; 25%). On T2-weighted MR images, SANTs displayed hypointensity in ten patients (10/12; 83.3%), isointensity in one patient (1/12; 8%) and hyperintensity in one patient (1/12; 8%). On T2-weighted images, stellate or scattered fibrous scars were observed in all patients (12/12; 100%). On diffusion-weighted images, SANTs appeared as heterogenous or homogeneous hypointense in 12 patients (12/12; 100%). Compared to out-of-phase images, SANTs displayed decreased local signal intensity on in-phase images in 12 patients (12/12; 100%). On enhanced CT and MRI images, SANTs had clear boundaries (17/18; 94%), oval (7/18; 39%) or lobular (7/18; 39%) shape, displayed progressive centripetal enhancement (18/18; 100%), spoke-wheel pattern (14/18; 78%), nodular enhancement (11/18; 61%), or delayed enhancement of central fibrous scar (9/18; 50%). CONCLUSIONS: SANT of the spleen predominantly manifests as a solid, single, oval or lobular, and well-defined lesion with a fibrous scar and occasional calcification. Typical enhancement characteristics include progressive and centripetal enhancement, spoke-wheel pattern, nodular enhancement, and delayed enhancement of central fibrous scar. Hypointensity on T2- and diffusion-weighted images are due to hemosiderin deposition and fibrous tissue.