Tsukasa Inoue

Progesterone receptor isoforms A and B in human epithelial ovarian carcinoma: immunohistochemical and RT-PCR studies

Human epithelial ovarian carcinoma is well-known as a sex steroid-dependent neoplasm, but the possible biological significance of progesterone receptor (PR) in this cancer remains controversial. Recently, two isoforms of human PR, PRA and PRB, have been characterized and different functional characteristics have been reported for these two isoforms. We therefore examined immunohistochemistry (107 cases) and reverse transcription-polymerase chain reaction (RT-PCR) (16 cases) for PRA, PRB, and oestrogen receptor-a (ER-a). Labeling indices (LI) for PRA and PRB were 2.4 and 43.6, respectively, and the difference was statistically significant. PRB LI, but not PRA LI, as well as performance status, stage, and residual tumour turned out to be independent prognostic factors following multivariate analysis. There was also a significant correlation between ER-a LI and PRB LI (r = 0.595, P < 0.0001), suggestive of a possible interaction between these two receptors. RT-PCR also detected the expression of PR isoform transcripts in the same pattern as was observed with immunohistochemistry. Results of these studies indicate that PRA and PRB both mediate distinct pathways of progesterone action in ovarian carcinoma. Moreover, it is important to examine PRB LI as a prognostic factor in the cases of human epithelial ovarian carcinoma.

Progesterone Receptor A and B Isoforms in the Human Breast and Its Disorders

Two different isoforms of progesterone receptor (PR), PRA and PRB, are expressed in target tissues at comparable levels. In this study, we first examined PRA and PRB immunoreactivity in human breast cancer and various intraductal proliferative epithelial lesions, and correlated these findings with clinicopathologic parameters. We then examined mRNA expression of PRA and PRB in six cases of invasive ductal carcinoma using RT‐PCR. Immunoreactivity for both PRA and PRB was positive in the great majority of proliferative disease without atypia (PDWA) (85% for PRA and 96% for PRB) and atypical ductal hyperplasia (ADH) (100% for PRA and 100% for PRB), but the ratio of immunopositive cases and immunohistochemical (IHC) scores was significantly smaller in ductal carcinoma in situ (DCIS) (65% for PRA and 75% for PRB) and invasive ductal carcinoma (IDC) (66% for PRA and 55% for PRB) than in PDWA and ADH. There was a significant positive correlation between IHC scores for PRA and estrogen receptor α (ERα) in IDC, DCIS and ADH but not between PRB and ERα. In IDC, both PRA and PRB IHC scores were significantly associated with histological grade, but there was no association between PRA or PRB status and lymph node involvement, tumor size, or prognosis of the patients. The expression of mRNAs for both PRA and PRB was detected in all six cases of IDC examined. These results suggest that both PRA and PRB are strongly associated with ERa in human breast and this relation may be disturbed in breast cancer.

A new technique of thoracoscopic pleurodesis for refractory hepatic hydrothorax.

Background: Hepatic hydrothorax is defined as a pleural effusion that arises in patients with cirrhosis of the liver and no cardiopulmonary disease; it is believed to result from peritoneopleural communication through a defect in the diaphragm. Methods: Nine patients underwent thoracoscopic pleurodesis. The diaphragmatic defect was detected and corrected in two cases. In all patients, an argon beam coagulator was applied to the diaphragm surface, which was then completely covered with bioabsorbable prostheses. We then spread 3 ml of fibrin glue on the covered diaphragm and sprinkled 5 KE of OK-432 and 100 mg of minocycline hydrochloride in the thoracic cavity. Results: All patients showed clinical improvement. The pleural effusion and breathlessness resolved immediately after pleurodesis. There were two recurrences after 1 and 4 months, respectively. One of these patients improved after repeat pleurodesis; the other was treated conservatively. Conclusion: Our new technique of thoracoscopic pleurodesis is an effective and minimally invasive treatment for patients with refractory hepatic hydrothorax.

Spatial and topological distribution of progesterone receptor A and B isoforms during human development.

Progesterone receptor (PR) is a member of the nuclear receptor superfamily. To date, two isoforms of PR have been identified, PR-A and PR-B. In progesterone responsive tissues, the relative ratio of PR-A and PR-B is considered to contribute to the tissue-specific actions of progesterone. In this study, we examined the distribution of PR-A and PR-B in human fetal tissues ranging from 11 to 40 gestational weeks using immunohistochemistry and RT-PCR analysis. PR immunoreactivity was detected in a wide range of fetal tissues until 20 weeks of gestation, but gradually decreased towards the late gestational period. However, PR continued to remain positive throughout the gestational period in the interstitial cells of Cajal and endocrine tissues. PR-B was demonstrated as the predominant isoform in comparison to PR-A in all fetal tissues examined. These findings suggest that progesterone may be involved in the development of fetal organs throughout the gestational period.

Immunohistopathological and molecular genetic features of a case in which gastrointestinal stromal tumor recurred five times

Gastrointestinal stromal tumor (GIST) is a distinct group of mesenchymal neoplasms recently shown to exhibit differentiation toward interstitial cells of Cajal. Although previous studies have shown that the clinical outcome of patients with GIST is associated with mitotic activity, the proliferation index determined by the Ki‐67 labeling index, immunophenotype (CD34 and/or p53) and mutation in exon 11 of the c‐kit, a definitive discrimination between benign and malignant GIST has not yet been established. We report a patient in whom malignant GIST in the abdomen recurred five times. In this case, the primary GIST and the five recurrent GIST were associated with c‐kit immunoreactivity, but the mitotic index of the GIST tended to be increasingly higher with subsequent recurrences. Mutational analysis of the c‐kit revealed that the primary and recurrent GIST were mutant‐negative. These data indicated that ‘morphologically appearing benign’ tumors with lower proliferative parameters may also have the capacity of metastasis and recurrence.