Proteomic characterization identifies clinically relevant subgroups of soft tissue sarcoma.

Soft tissue sarcoma is a broad family of mesenchymal malignancies exhibiting remarkable histological diversity. We portray the proteomic landscape of 272 soft tissue sarcomas representing 12 major subtypes. Hierarchical classification finds the similarity of proteomic features between angiosarcoma and epithelial sarcoma, and elevated expression of SHC1 in AS and ES is correlated with poor prognosis. Moreover, proteomic clustering classifies patients of soft tissue sarcoma into 3 proteomic clusters with diverse driven pathways and clinical outcomes. In the proteomic cluster featured with the high cell proliferation rate, APEX1 and NPM1 are found to promote cell proliferation and drive the progression of cancer cells. The classification based on immune signatures defines three immune subtypes with distinctive tumor microenvironments. Further analysis illustrates the potential association between immune evasion markers (PD-L1 and CD80) and tumor metastasis in soft tissue sarcoma. Overall, this analysis uncovers sarcoma-type-specific changes in proteins, providing insights about relationships of soft tissue sarcoma.

Construction of a prognostic nomogram based on pathology for long-term survival after radical resection of intrahepatic cholangiocarcinoma / 中华肝胆外科杂志

Objective:To establish and evaluate a nomogram for long-term survival of patients with intrahepatic cholangiocarcinoma (ICC) after radical resection.Methods:The data of ICC patients who underwent radical resection for the first time at Zhongshan Hospital, Fudan University from January 2014 to December 2017 were retrospectively analyzed. Of 167 patients who were enrolled, there were 104 males and 63 females, with the age of (60.3±10.9) years. Tumor tissues were collected for immunohistochemical staining and interpretation. Univariate Cox regression, LASSO regression and multivariate Cox regression were used to analyze influencing factors of postoperative long-term survival after ICC. R software was used to construct a nomogram in predicting ICC prognosis.Results:Cox regression analysis showed that TNM staging, poorly differentiated tumor, positive resection margin, positive mucin 5 expression and abnormal P53 expression to be independent risk factors associated with poor long-term survival after radical resection. The prognostic nomogram model of ICC was constructed based on these factors. The C-index was 0.821. The nomogram model consistency index had a high degree of prognostic differentiation. The 45° diagonal of the 3-year postoperative calibration curve which represented the actual survival fitted well with the segmented line which represented the predicted survival of the nomogram. The area under the receiver operating characteristic curve of the nomogram model was higher than that of AJCC TNM staging (0.894 vs. 0.803, z=4.10, P<0.001). The nomogram model was more effective in predicting postoperative survival of ICC patients than the TNM staging. Conclusion:TNM staging, poorly differentiated tumor, positive resection margin, positive mucin 5 expression and abnormal P53 expression were independent risk factors for postoperative survival of ICC. The nomogram model could better evaluate long-term prognosis of ICC patients after radical resection than the traditional TNM staging system.

Hepatic angiomyolipoma: a clinicopathologic features and prognosis analysis of 182 cases / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathological characteristics of hepatic angiomyolipoma (HAML) and to evaluate the correlation between clinicopathological parameters and tumor subtypes.</p><p><b>METHODS</b>Retrospective analysis of clinicopathological features was conducted in 182 cases of HAML.</p><p><b>RESULTS</b>HAML patients were predominantly female (M:F=1:4) and most commonly presented with non-specific symptoms. The median age at diagnosis was 46 years, ranged from 17 to 77 years. Tumor diameter was ranged from 0.3 to 32.0 cm with an average of 5.0 cm. Majority of the tumor was epithelioid type (112/165, 67.9%). Extramedullary hematopoiesis, multinucleated giant cells, intranuclear inclusions, nucleolus, cellular atypia, invasive growth pattern, multiple masses, hyperpigmentation and purpura-like changes mostly occurred in the epithelioid type (P<0.05). Extramedullary hematopoiesis was commonly seen in HAML, the significance of which was still uncertain.</p><p><b>CONCLUSIONS</b>Most of HAML are epithelioid type, characterized by a proliferation of predominantly epithelioid cells, in which extramedullary hematopoiesis is commonly seen. Some morphologic features that may predict malignant such as necrosis, mitotic figures, and tumor emboli are only found in the epithelioid HAML. Mitotic activity, tumor necrosis, tumor thrombus, giant cells, periportal invasion, multiple lesions and tumors size over 10 cm are closely related with tumor recurrence and metastasis.</p>

The use of mutation-specific antibodies in predicting the effect of EGFR-TKIs in patients with non-small-cell lung cancer.

PURPOSE: We aimed to quantify the epidermal growth factor receptor (EGFR) mutation in tumors and to analyze its prediction of EGFR-tyrosine kinase inhibitor (EGFR-TKI) treatment efficacy in EGFR mutation-positive non-small-cell lung cancer (NSCLC) patients. METHODS: We examined EGFR mutation status in 124 lung cancer samples by direct sequencing and amplification refractory mutation system. Among them, 41 were appropriate to quantify the expression of mutant EGFR proteins using immunohistochemistry (IHC) with mutation-specific antibodies. The quantification was determined by both the staining intensity and the proportion of stained tumor cells. RESULTS: The median progression-free survival (PFS) in patients with a high score for mutant EGFR expression was 18.0 months (95 % CI 16.0-20.0), which was significantly longer than that in patients with a low score (8.0 months; 95 % CI 2.6-13.4; P = 0.048). Such significant association with patients' PFS was also apparent in the proportion of stained tumor cells (median, 19.0 vs. 8.0 months; P = 0.019), but not in the staining intensity (P = 0.787). Among the 41 specimens, 32 were detected EGFR mutation positive by both direct sequencing and ARMS, referring to a relatively high abundance of mutation, and 26 (81.3 %) of them gained a high expression score of mutant proteins as well. Six samples with mutation negative by direct sequencing but positive by ARMS, which showed a low abundance, and 5 (83.3 %) of them also revealed a low expression score. The EGFR mutation quantitative analysis using mutation-specific IHC was moderately consistent with that by molecular-based assays (P = 0.001, kappa value 0.50). CONCLUSIONS: Our results suggest that immunohistochemical analysis with mutation-specific antibodies is a promising approach for quantifying EGFR mutations, and may predict the effect of EGFR-TKI treatment for EGFR mutation-positive NSCLC.

[Screening of differentially expressed microRNAs in borderline and malignant gastrointestinal stromal tumors].

OBJECTIVE: Gastrointestinal stromal tumors (GISTs) have a broad spectrum of biological behaviors ranging from benign, borderline and malignant. This study aimed to screen differentially expressed microRNAs (miRNAs) between malignant and borderline GISTs and to investigate the potential role of miRNAs in the malignant transformation of GISTs. METHODS: Six GIST samples including borderline tumors (n = 3) and malignant tumors (n = 3) were collected based on the clinical and pathological characteristics. Total RNA was extracted, followed by miRNA microarray analysis to screen the differentially expressed miRNAs. The most significantly expressed 4 miRNAs were then chosen for further validation by real-time PCR in 22 additional GIST samples. RESULTS: Direct comparison of malignant group versus borderline group revealed 14 significantly and differentially expressed miRNAs (P < 0.05, with a fold change of < 0.5 or > 2). Five miRNAs were up-regulated and nine were down-regulated in the malignant group. Four miRNAs (miR-221, miR-135b, miR-675(*) and miR-218) were most significantly and differentially expressed between the two groups. The differential expression of 2 miRNAs (miR-221 and miR-675(*)) were subsequently confirmed with good concordance by real-time PCR. CONCLUSIONS: The differential miRNA expression profiles between two groups are revealed by miRNA microarray assay, and confirmed by real-time PCR. Among differentially expressed miRNAs, miR-221 and miR-675(*) might be related to the malignant transformation of GISTs, and have a potential value in predicting biological behavior of GISTs.

Primary and metastatic hepatic neuroendocrine carcinoma: a clinicopathological study / 中华肝胆外科杂志

Objective To study the clinicopathological features of primary and metastatic hepatic neuroendocrine carcinoma.Methods The records of 35 patients with primary hepatic neuroendocrine carcinoma and 35 patients with metastatic hepatic neuroendocrine carcinoma were retrospectively reviewed.These patients served as the primary group(priNET,n=35)and the metastasis group (metNET,n=35),respectively.Results There were significant differences between the two groups of patients in gender,site,size and number of tumor(P＜0.05).Although there was no significant difference between the two groups in the distribution of the tumors in the two lobes of liver (P＞0.05),priNET had more tumors localized to one lobe of liver while metNET had more tumors involving both lobes of liver(P＜0.05).Conclusions Gender,size,site and number of tumor may play an important role in the differentiation of primary or metastatic hepatic neuroendocrine tumor.

Therapy-related acute myeloid leukemia in a primary pulmonary leiomyosarcoma patient with skin metastasis.

Primary pulmonary leiomyosarcoma (LMS) is a very unusual tumor. Although LMS has well-known metastatic potential, cutaneous metastasis is a remarkably uncommon. Exposure to cytotoxic agents could lead to "therapy-related myeloid neoplasm" (t-MN). Starting from 2008, the World Health Organization (WHO) has adopted the term to cover the spectrum of malignant diseases previously known as therapy-related acute myeloid leukemia (t-AML), therapy-related myelodysplastic syndrome (t-MDS) and therapy-related myelodysplastic/myelo- proliferative neoplasm (t-MDS/MPN). We described the onset of t-MDS and progression to t-AML in one case diagnosed as primary pulmonary LMS with cutaneous metastasis. This patient achieved complete remission (CR) after three courses of IA regimen chemotherapy (idarubicin 5 mg/d, d 1-3; cytarabine 100 mg/d, d 1-5) and 1 course of HA chemotherapy regimen (homoharringtonine 3 mg/d, d 1-3; cytarabine 100 mg/d, d 1-7). This case presents the natural course of therapy-related neoplasm and provides therapeutic experience for t-AML.

Focal nodular hyperplasia of liver: a clinicopathologic study of 238 patients / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features of focal nodular hyperplasia (FNH) of liver.</p><p><b>METHODS</b>The clinical, radiologic, pathologic findings and follow-up data of 238 cases of FNH were retrospectively analyzed.</p><p><b>RESULTS</b>The patients included 93 females and 145 males. The age of the patients ranged from 11 to 77 years (median = 39.1 years). Amongst the 233 patients who had clinical information available, 188 were asymptomatic, 216 had no history of hepatitis B and/or C infection and 232 had negative serum alpha-fetoprotein level. Amongst the 185 patients who had undergone radiologic examination, 123 (66.5%) were accurately diagnosed as such. Macroscopically, of the 284 lesions from 238 patients, the average diameter was 3.7 cm. Two hundred and fifteen cases (90.3%) were solitary, 172 cases were located in the right lobe and 115(40.5%) had central stellate fibrotic scars or lobulated cut surface. Histologically, 229 lesions belonged to classic type and 9 lesions were of non-classic type. The latter was further classified as the telangiectatic form (6 lesions) and the mixed hyperplastic and adenomatous form (3 lesions). There was no evidence of significant cytologic atypia. Follow-up data were available in 173 patients (72.7%). None of them died of the disease and 2 patients suffered from relapses after 2 and 4 years, respectively.</p><p><b>CONCLUSIONS</b>FNH is a hyperplastic response of normal liver cells to local blood flow anomalies. It has no obvious sex predilection and more than 66% can be diagnosed accurately with radiologic examination. The lesions in the current study show no cytologic atypia.</p>

Melanotic epithelioid clear cell tumor of kidney: report of three cases / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the pathologic features and immunophenotype of 3 cases of melanotic epithelioid clear cell tumor of kidney.</p><p><b>METHODS</b>More than 2000 cases of renal tumors were retrospectively reviewed. Three cases of melanotic epithelioid clear cell tumor were identified. Immunohistochemical study was carried out using the paraffin-embedded tissue samples. Electron microscopy was also performed in 1 case.</p><p><b>RESULTS</b>Amongst the 3 cases studied, the male-to-female ratio is 1:2. Histologically, 2 cases showed a clear cell carcinoma-like pattern. Papillary structures covered by clear cells and eosinophilic cells were observed in 1 case. Immunohistochemical study showed that the tumor cells in all cases expressed HMB 45. Two of them were also positive for Melan A. The staining for epithelial markers and S-100 protein was negative. Melanosomes were not identified by ultrastructural examination.</p><p><b>CONCLUSIONS</b>Melanotic epithelioid clear cell tumor is a rarely seen neoplasm of kidney. There are some histologic overlaps with renal cell carcinoma, epithelioid angiomyolipoma and melanoma. Immunohistochemical study is useful in confirming the diagnosis. The tumor represents a morphologic variant of epithelioid angiomyolipoma.</p>

Imatinib mesylate STI571 therapy for five patients with advanced gastrointestinal stromal tumors / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the therapeutic effect of STI571(imatinib mesylate) on advanced gastrointestinal stromal tumors (GISTs).</p><p><b>METHODS</b>Clinical data of 5 cases with advanced GISTs were analyzed retrospectively.</p><p><b>RESULTS</b>The expression of c- kit (CD117) was detected by immunohistochemical method in five patients with advanced GISTs . All patients failed to systematic chemotherapy or radiofrequency and operation because of extensive and multiple metastases (4 cases underwent 1 to 3 times of exploratory surgery). Tumor size was markedly decreased one to six months after STI571 given without serious drug- related side effects.</p><p><b>CONCLUSIONS</b>STI571 is an effective chemotherapy for advanced unresectable or metastatic GISTs. Inhibitor of the Kit signal- transduction pathway is a promising regimen that is different from conventional chemotherapy for advanced GISTs.</p>