Atsumi Kojima

Gastric morphology and immunophenotype predict poor outcome in mucinous adenocarcinoma of the uterine cervix

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.

Absence of High-Risk Human Papillomavirus (HPV) Detection in Endocervical Adenocarcinoma with Gastric Morphology and Phenotype

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 PCR-based 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 p16INK4a, 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.

Eradication and reinfection of human papillomavirus after photodynamic therapy for cervical intraepithelial neoplasia.

AbstractBackground. Photodynamic therapy (PDT) has been proven to be a promising therapeutic modality for selected dysplasias and malignancies in a variety of organs. We assessed the effectiveness of PDT for treating cervical intraepithelial neoplasia (CIN) by cytological and histological examinations and investigated its impact on human papillomavirus (HPV) infection. Methods. A series of 31 patients with CIN (2 with CIN2, 29 with CIN3) were given polyhematoporphyrin ether/ester (PHE) 2 mg/kg IV. After 60 h their cervices were exposed to a 630-nm YAG-OPO laser. HPV-DNA extracted from cervical smears was amplified by the polymerase chain reaction and typed for HPV using restriction fragment length polymorphism. Results. At 3 months after PDT, cytology and directed biopsy of the cervix revealed regression of the disease in 28 [complete remission (CR) rate 90%] of 31 patients, and HPV-DNA could be no longer detected in the cervical smears of 22 (76%) of 29 HPV-positive patients. After 12 months, all 31 patients had achieved a CR on biopsy, although HPV-DNA was still present in the cervical smears of 6 patients. The types of HPV-DNA detected 12 months after PDT were different from those seen before PDT in each of the 6 patients, suggesting that they might be reinfected with other HPV types after PDT. Conclusion. PDT is effective not only in improving the cytological and histological measures when treating CIN but also for eradicating cervical HPV.

Diagnostic reproducibility in gastric-type mucinous adenocarcinoma of the uterine cervix: Validation of novel diagnostic criteria

Service Central d’anatomie et de cytologie pathologiques, Hôpital Hotel-Dieu, place du Parvis Not re-Dame, F 75181 Paris cedex 04, Service Central d’anatomie et de cytologie pathologiques, Hôpital Henri-Mondor, F 94010 Creteil cedex, Service Central d’anatomie pathologique, Centre Hospitalo-universitaire, F 29609 Brest cedex, and Service de Pathologie, Groupe Hospitalier Paris Saint-Joseph, F 75674 Paris cedex 14

Establishment and characterization of a human cell line derived from a uterine papillary serous carcinoma with wild-type p53 function

Uterine papillary serous carcinoma is an uncommon histologic subtype of endometrial cancer that behaves aggressively and has a poor prognosis. We successfully established a uterine papillary serous carcinoma cell line. The population-doubling time was approximately 16 h. Although loss of p53 function is considered critical for the molecular pathogenesis of uterine papillary serous carcinoma, p53 was not only mutated but functionally active in this cell line. This newly established cell line should be useful for investigating the characteristics of uterine papillary serous carcinoma.