Hiromitsu Yamakawa

Infrequent genetic alterations of the PTEN/MMAC1 gene in Japanese patients with primary cancers of the breast, lung, pancreas, kidney, and ovary

In the present study, we searched for genetic alterations of the entire coding region of PTEN/MMACl, a recently isolated candidate tumor suppressor gene, in 178 specimens from Japanese patients with various malignant tumors by the polymerase chain reaction‐single strand conformation polymorphism method. The samples consisted of 11 glioblastoma multiformes (GBMs), 14 astrocytomas, 47 breast cancers, 25 non‐small cell lung cancers, 9 small cell lung cancers, 8 pancreatic cancers, 24 renal cell carcinomas, 20 ovarian cancers, and 20 metastatic lung tumors from various organs. Only one somatic frameshift mutation at codon 319 was observed in one (9%) of eleven GBMs. Our results suggest that mutation of the PTEN/MMAC1 gene does not play a major role in carcinogenesis, at least in the tumor types from Japanese patients analyzed in this study.

The PTEN, BAX, and IGFIIR Genes Are Mutated in Endometrial Atypical Hyperplasia

To pursue the pathogenesis of endometrial carcinogenesis, we investigated microsatellite instability, mutations in the PTEN, TGFβRII, IGFIIR, and BAX genes, and LOHs on 10q in 18 putative endometrial premalignant lesions (11 endometrial atypical hyperplasias (ATHs), 2 complex hyperplasias, and 5 simple hyperplasias) as well as 8 endometrial cancers (ECs). In the ATH cases, MSIs as well as LOHs at 10q were observed at frequencies similar to those in ECs. Mutations in PTEN, BAX, and IGFIIR were observed only in ATHs and ECs. These results suggest that (1) PTEN, BAX, and IGFIIR are already mutated in ATHs, and (2) ATH is one of the precursor lesions which could lead to EC.

Identification of a 100‐kb region of common allelic loss on chromosome bands 10q25–q26 in human endometrial cancer

In human endometrial cancer, we have previously identified a 790‐kb region of common allelic loss in chromosome bands 10q25–q26, flanked by D10S587 and D10S1723. We constructed a contig covering the entire deleted region using YACs, PACs, and BACs. Five overlapping cosmid clones derived from YAC clones completely covered the entire deleted region: its size was estimated to be no larger than 200 kb. We further performed two‐color fluorescence in situ hybridization (FISH) analysis to confirm the deletion and narrowed down the deleted region to 100 kb or less; it was covered by three overlapping cosmid clones that were included in one BAC clone. Restriction endonuclease mapping identified a region in which NotI, SalI, SmaI, and XhoI were clustered, suggesting the possible existence of a CpG island. Genes Chromosomes Cancer 23:74–77, 1998.

Conization by Harmonic Scalpel for Cervical Intraepithelial Neoplasia: A Clinicopathological Study

The Harmonic Scalpel® (HS) is a new surgical tool that cuts and coagulates by converting electrical energy into ultrasonic mechanical vibrations. The purpose of our study was to compare HS conization and the loop electrosurgical excision procedure (LEEP) for cervical intraepithelial neoplasia (CIN) with respect to both clinical and pathological features. Fifty-one consecutive women conservatively treated (29 with LEEP and 22 with HS conization) for CIN III were retrospectively reviewed. The background of the patients was similar. Operative time, intra- and postoperative blood loss were not significantly different. With HS conization all specimens were removed in one piece, but with LEEP the median number of specimens obtained per patient was 3.3 (p < 0.0001) with a maximum of 5. The depth of thermal artifacts at the endocervical margin was significantly less with HS conization (0.20 mm) than with LEEP (0.30 mm; p = 0.0006). This new method produced an ideal-shaped specimen without increasing complications and thermal artifacts compared with LEEP.

Identification of a 100-kb region of common allelic loss on chromosome bands 10q25-q26 in human endometrial cancer

In human endometrial cancer, we have previously identified a 790-kb region of common allelic loss in chromosome bands 10q25-q26, flanked by D10S587 and D10S1723. We constructed a contig covering the entire deleted region using YACs, PACs, and BACs. Five overlapping cosmid clones derived from YAC clones completely covered the entire deleted region: its size was estimated to be no larger than 200 kb. We further performed two-color fluorescence in situ hybridization (FISH) analysis to confirm the deletion and narrowed down the deleted region to 100 kb or less; it was covered by three overlapping cosmid clones that were included in one BAC clone. Restriction endonuclease mapping identified a region in which NotI, SalI, SmaI, and Xhol were clustered, suggesting the possible existence of a CpG island.

Tumor angiognesis, hepatocyte growth factor, and c-Met expression in endometrial carcinoma

BACKGROUND This study was designed to evaluate the significance of tumor angiogenesis and angiogenic factors such as hepatocyte growth factor (HGF) and c-Met in determining the prognoses of 93 patients with endometrial carcinoma. METHODS By immunohistochemical staining, this retrospective study investigated tumor angiogenesis, HGF expression, and c-Met expression, using one tissue slide that was representative of the invasive edge of the tumor. To evaluate tumor angiogenesis, the microvessels within the primary endometrial carcinoma were highlighted by staining their endothelial cells immunohistochemically for von Willebrand factor (VWF). The microvessels were then counted in the most intense areas of neovascularization. HGF and c-Met were identified with specific antibodies. Tumor angiogenesis, HGF expression, and c-Met expression were correlated with both the prognostic variables for and the survival of endometrial carcinoma. RESULTS A high microvessel count (> or = 110 in a 0.90 mm2 area) was significantly correlated with surgical Stage III and IV, histologic Grade 3, positive lymph node involvement, and shorter patient survival. Expression of c-Met was significantly correlated with surgical Stage III and IV, histologic Grade 3, and shorter survival. HGF expression was significantly correlated with surgical Stage III and IV by semiquantitative analysis. Multivariate analysis showed that surgical Stage III and IV, histologic Grade 3, the score for myometrial invasion > 1/2, and a high microvessel count were independent indicators of the prognoses of patients with endometrial carcinoma. CONCLUSIONS Both tumor angiogenesis, measured by the microvessel count, and c-Met expression were significant prognostic indicators for patients with endometrial carcinoma.