Endocervical-type mucinous adenocarcinoma (ECA) of the uterine cervix is defined as a tumor composed of cells resembling those of the endocervical glands, but recent studies have demonstrated that a minority of ECAs displays a gastric immunophenotype. The aim of this study was to assess the significance of the gastric phenotype. Fifty-three cases of mucinous adenocarcinoma of the uterine cervix (37 FIGO stage IB, 4 stage IIA, and 12 stage IIB) were reviewed and reevaluated using a newly established morphologic criteria for distinguishing gastric type adenocarcinoma, which was defined as a tumor showing clear and/or pale eosinophilic and voluminous cytoplasm, with distinct cell borders. The results were correlated with gastric immunophenotype, determined by HIK1083 and MUC6 immunostaining, and patient outcome. Following the current World Health Organization scheme (2003), 47 tumors (89%) were classified as ECA, 1 (2%) as intestinal type, 1 (2%) as mixed endocervical and intestinal type, and 4 (8%) as minimal deviation adenocarcinoma. Twelve of 47 (26%) ECAs and all 4 minimal deviation adenocarcinomas, reclassified as gastric type using the novel criteria, were frequently positive for HIK1083 with a rate of 75% (12/16), whereas only 11% (4/37) of nongastric tumors were positive. There was no significant difference in MUC6 reactivity between gastric and nongastric type tumors (31%, 5/16 vs. 16%, 6/37; P=0.4). Patients with gastric-type adenocarcinomas had a significantly decreased 5-year disease-specific survival rate (30 vs. 77%; P<0.0001), and the gastric type morphology was related to a significant risk for disease recurrence compared with the nongastric type (P=0.001; HR, 4.5; 95% confidence interval, 1.42-14.2). HIK1083-positivity was also related to decreased 5-year disease-specific survival rate (38% vs. 74%; P<0.005). Mucinous adenocarcinoma of the uterine cervix with gastric immunophenotype can be a distinct morphologic variant showing an aggressive clinical course.

GAS showed aggressive behavior with ominous histopathological predictors as well as decreased survival.• GAS also showed resistance to radiotherapy.• GAS is therefore considered a distinct entity that should be distinguished from UEA. a b s t r a c tObjective. Gastric-type mucinous carcinoma (GAS) is a novel variant of mucinous carcinoma of the uterine cervix. As shown in the original Japanese group description, in recent studies, GAS represents a more aggressive disease than the usual-type endocervical adenocarcinoma (UEA). Detailed clinicopathological features of this variant remain to be elucidated in a larger series of patients.Methods. Patients were enrolled by the Gynecologic Cancer Study Group of the Japan Clinical Oncology Group after receiving the approval of each Institutional Review Board. The study population comprised of women with stage I to II endocervical adenocarcinomas who underwent surgery between 2000 and 2009. Representative slides were evaluated by central pathological review (CPR), categorized into either GAS or UEA, and correlated with clinicopathological features and outcome.Results. Among the 393 enrolled patients with endocervical adenocarcinoma, 328 patients met the criteria for CPR and the study eligibility criteria and were included in further analysis. A total of 95 of the 328 tumors were classified as GAS. Compared with UEA, GAS was more significantly associated with bulky mass, deep stromal invasion, lymphovascular space invasion, parametrial invasion, ovarian metastasis, positive ascitic fluid cytology, j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / y g y n o pelvic lymph node metastasis, and pathological (p) T stage but was not related to the degree of histological differentiation. Disease-free survival (P b 0.0001) and overall survival (P b 0.0001) were poorer in patients with GAS than in those with UEA.Conclusions. GAS showed aggressive behavior with ominous histopathological predictors as well as decreased survival. GAS is therefore considered a distinct entity that should be distinguished from UEA.Clinical trial information. UMIN Clinical Trials Registry: UMIN000007987

A subset of endocervical-type mucinous adenocarcinomas (ACs) of the uterine cervix exhibit a gastric phenotype and morphology, as reported in cases of minimal deviation AC in which the presence of human papillomavirus (HPV) has been rarely detected. To investigate the HPV-independent pathway of carcinogenesis in cases of gastric-type AC, we investigated the common high-risk HPV (hr-HPV) status in 52 nonsquamous cell carcinomas , using a PCRbased typing method and immunohistochemistry of p16INK4a (a cyclin-dependent kinase inhibitor that is overexpressed in both cancerous and precancerous cervical tissue, making it an ideal biomarker for cervical cancer cases). Using novel morphological criteria, seven of 52 (13.5%) carcinomas were designated as gastric-type ACs, all of which were negative for both hr-HPV DNA and p16INK4a . Nongastric-type ACs were frequently positive for both hr-HPV DNA (90%, 28/31) and p16INK4a (94%, 29/31) with adenosquamous and neuroendocrine carcinomas demonstrating the presence of hr-HPV DNA in 86% (6/7) and 83% (5/6) of cases , respectively. In these two types of carcinoma , 86% (6/7) and 100% (6/6) were positive for p16 INK4a , respectively. Our data suggests that gastric-type AC appears to represent an oncogenic hr-HPV-independent neoplasm and therefore is a potential pitfall of HPV DNA testing and vaccination.

These findings suggest that GAS should be distinguished from UEA by its chemoresistance, necessitating an alternative treatment strategy established for this distinct subtype of endocervical adenocarcinoma.

Maximum SUV on preoperative FDG-PET/CT in ovarian epithelial cancer differs according to histologic type. In clear cell AC, SUVmax may represent a prognostic factor.

Using patient questionnaires, we studied the long-term effect of leaving the peritoneum open on the incidence of lymphedema of the legs in patients following pelvic lymphadenectomy for gynecological malignancies. The patients were retrospectively assigned to one of two groups, depending on whether the retroperitoneum was closed or left open at surgery. Three years after surgery, we obtained valid questionnaire responses from 101 patients (43 cervical, 46 endometrial, and 12 ovarian cancers) in the closure group and 83 patients (34 cervical, 40 endometrial, and 9 ovarian cancers) in the nonclosure group. In patients' self-analysis, the overall incidence of lymphedema of the legs was significantly lower in the nonclosure group than in the closure group (25.3% and 50.5%, respectively; P<0.01). The incidence of lymphedema of the legs was significantly increased by postoperative radiotherapy. Especially in the nonclosure group, the incidence of lymphedema was only 15.8% in patients who did not have radiotherapy, but it increased significantly (44.4%) (P<0.05) when patients underwent radiotherapy. In conclusion, this questionnaire survey suggested that leaving the retroperitoneum open after lymphadenectomy is significantly effective in reducing the incidence of leg lymphedema, which impairs patients' quality of life more than expected by physicians.

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Calcification of bioprosthetic valves (BVs) implanted in aortic position can result in gradual deterioration and necessitate aortic valve replacement. The molecular mechanism of calcium deposition on BV leaflets has been investigated, but remains to be fully elucidated. The present study aimed to identify explanted bioprosthetic valve (eBV)-specific proteins using a proteomics approach and to unveil their biochemical and histological involvements in calcium deposition on BV leaflets. Calcification, fibrosis, and glycosylation of the valves were histologically assessed using Von Kossa, Masson's Trichrome and Alcian Blue staining, as well as immunostaining. Protein expression in the explanted biological valves was analysed using proteomics and western blotting. In a histological evaluation, αSMA-positive myofibroblasts were not observed in eBV, whereas severe fibrosis occurred around calcified areas. SDS-PAGE revealed three major bands with considerably increased intensity in BV leaflets that were identified as plasminogen and fibrinogen gamma chain (100 kDa), and fibrinogen beta chain (50 and 37 kDa) by mass analysis. Immunohistochemistry showed that fibrinogen β-chain was distributed throughout the valve tissue. On the contrary, plasminogen was strongly stained in CD68-positive macrophages, as evidenced by immunofluorescence. The results suggest that two important blood coagulation-related proteins, plasminogen and fibrinogen, might affect the progression of BV degeneration.