Akiharu Okamura

Cyclin-D1-gene amplification is a more potent prognostic factor than its protein over-expression in human head-and-neck squamous-cell carcinoma.

To evaluate the prognostic significance of cyclin D1 protein/gene expressions in human head‐and‐neck squamous‐cell carcinoma (HNSCC), we examined amplification of the cyclin‐D1 gene (CCND1) by the differential PCR method and over‐expression of cyclin‐D1 protein by immunohistochemistry in 45 paraffin‐embedded sections from HNSCC. Amplification of CCND1 was found in 10 (22%) cases and over‐expression of cyclin D1 was found in 24 (53%) cases. CCND1 amplification was also found in 3 (25%) of 12 cases of dysplastic lesions adjacent to HNSCC. The overall 5‐year survival of patients with CCND1 amplification or with protein over‐production was significantly lower than that of patients without (p < 0.0001 and p < 0.05, respectively). However, with multivariate analysis, only amplification of CCND1 retained an independent prognostic value (p = 0.0018). These suggest that CCND1 amplification occurs at early stages of HNSCC tumorigenesis and is a more useful prognostic factor than over‐expression of cyclin D1 in HNSCC. Int. J. Cancer 74:576–581, 1997.© 1997 Wiley‐Liss, Inc.

EPSTEIN-BARR VIRUS RELATED GASTRIC CANCER IN JAPAN : A MOLECULAR PATHO-EPIDEMIOLOGICAL STUDY

Epstein‐Barr virus (EBV) involvement in gastric carcinoma has been demonstrated by the presence of EBV genomes and EBV‐encoded small RNA (EBER) in the carcinoma cells, monoclonal proliferation of EBV‐infected carcinoma cells and elevated antibody titers. The present study was conducted to investigate the prevalence of EBV involvement among gastric carcinomas observed in nine Japanese cities with varying gastric cancer rates. In situ hybridization of EBER‐1 was applied to paraffin sections from 1848 carcinomas observed in 1795 cases and EBV involvement was detected based on uniform hybridization in carcinoma cells. Epstein‐Barr virus was detected in 6.6% of lesions and 6.7% of cases. The rate of EBV involvement did not vary significantly for each city and there was no correlation with underlying gastric cancer mortality rates. Thus, geographic variation of gastric cancer rates within Japan cannot be explained in terms of EBV involvement. Epstein‐Barr virus‐related gastric carcinoma is one of the most common EBV‐related tumors in Japan. The involvement of EBV was significantly more frequent among males than among females, mainly for cancers occurring in the upper and middle part of the stomach, and exhibited more variation by cell type among males. These observations suggest that other factors yet to be discovered may modulate the causal role of EBV in gastric carcinogenesis.

Keratin profiles in normal/hyperplastic prostates and prostate carcinoma

Immunoreactivities in 25 cases of prostatic adenocarcinoma and 10 normal/hyperplastic prostates were investigated in methacarn-fixed, paraffin-embedded serial sections using a panel of nine anti-keratin monoclonal antibodies (mAbs); 34β E12, CK8.12, 312C8-1, CK4.62, RPN1165, RPN1162, 35βH11, CK5, M20, and one of anti-actin mAb, HHF35. In normal/ hyperplastic prostates, RPN1162, 35βH11, CK5 and M20 stained luminal cells without staining basal cells, and 34βE12, CK8.12 and 312C8-1 stained basal cells but not luminal cells. Other mAbs, CK4.62 and RPN1165, stained basal cells as well as luminal cells. All of the mAbs labelling luminal cells stained cancer cells with variable frequencies in a manner unrelated to the grade of tumour differentiation. Of the prostate cancer cases 92% were scored positive with M20, 84% with 35βH11, 80% with CK5, 68% with CK4.62, 60% with RPN1165 and 4% with RPN1162. However, basal cell-specific keratins labelled with 34βE12, CK8.12 and 312C8-1 were totally negative in the cancer cells. HHF35 showed no labelling in normal, hyperplastic or neoplastic epithelial cells of the prostate. Our findings indicate that the major part of the cells of prostatic adenocarcinomas have keratin phenotypes similar to luminal cells but not basal cells, and that no myoepithelial differentiation can be detected in epithelial cell of the prostate. Thus, mAbs for keratins facilitate the identification of epithelial cell phenotypes in normal, benign and malignant conditions of the prostate.

Down-regulation of TGF-β receptors in human colorectal cancer : implications for cancer development

Many colorectal cancer cells are resistant to the anti-proliferative effects of transforming growth factor-β (TGF-β). TGF-β also acts as paracrine factor from cancer cells on their mesenchymal cells. The aim of this study was to examine the expression of TGF-β and its receptors in human colorectal cancer tissue and determine any relationship with cancer growth. In situ hybridization and Northern blot hybridization detection of TGF-β1, type I and type II receptor mRNA and immunohistochemical staining of TGF-β1 were performed using 11 human colorectal adenomas, 22 colorectal cancers and ten normal colorectal mucosas as control. TGF-β receptor mRNAs were expressed mainly by normal colorectal epithelial cells and adenoma. However, mRNAs for TGF-β receptors were only faintly, if at all, expressed in eight of 22 human colorectal cancers. In addition, intense signals of TGF-β1 mRNA and the protein were detected in all colorectal cancers. TGF-β receptor mRNAs and TGF-β1 protein were also distributed in fibroblasts and endothelial cells in the interstitium. Moreover, Smad 4 protein was translocated to nucleus in primarily cultured adenoma cells, but not in cancer cells after TGF-β stimulation. The escape of human colon cancer from TGF-β -mediated growth inhibition by down-regulation of TGF-β receptors as well as the effects of TGF-β on stroma formation and angiogenesis indicate a possible role for TGF-β in the progression of colon cancer in an intact host.

Prognostic significance of p53, Ki-67, VEGF and Glut-1 in resected stage I adenocarcinoma of the lung

OBJECTIVES The purpose of this study was to evaluate the prognostic significance of various biological factors in patients with resected stage I adenocarcinoma. METHODS We immunohistochemically examined 47 specimens of surgically resected adenocarcinomas to evaluate the expression of the biological markers p53, Ki-67, vascular endothelial growth factor (VEGF) and glucose transporter-1 (Glut-1). Angiogenesis grade and tumor vessel invasion was also investigated. Actuarial survival was analyzed by the Kaplan-Meier method. Clinical variables and biological markers were analyzed using the Coxs proportional hazards model for multivariate analysis to identify independent prognostic factors. RESULTS The overall survival rate for the whole series was 85.1% at 3 years and 71.9% at 5 years, with a median survival time of 73 months. Differentiation, Ki-67, Glut-1, VEGF, tumor vessel invasion and microvessel density (MVD) were significant prognostic factors by univariate analysis, with Glut-1 expression the most important prognostic factor for survival (P<0.0001). After multivariate analysis, only Glut-1 expression remained as a prognostic factor for survival. CONCLUSION Glut-1 expression can be a predictor for prognosis in patients with resected stage I adenocarcinoma of the lung.

Multiple Hepatoblastomas Associated with Trisomy 18 in a 3-Year-Old Girl

A very rare case of full trisomy 18 associated with multiple hepatoblastomas is reported. The patient also had ventricular septal defect and patent ductus arteriosus, which were repaired at 6 months of age. After the cardiac surgery, she was noted to have an abdominal mass and an elevated serum alpha-fetoprotein level. A partial hepatic lobectomy was performed at 7 months of age, and the resected tumor was diagnosed as a fetal-type hepatoblastoma. At 2 years and 4 months of age, a chest radiography disclosed an elevated left diaphragm, and abdominal ultrasonography demonstrated a tumor in the left hepatic lobe. The resected tumor was also diagnosed as a fetal-type hepatoblastoma. Chromosomal analysis demonstrated that the karyotypes of peripheral blood and hepatic tumor cell obtained on two occasions were both 47,XX, +18. She has no evidence of recurrence at 3 years of age without specific therapy.

A correlation of argyrophilic nucleolar organizer regions with stages of hepatocellular carcinoma

Background. Recently, the number and morphologic features of argyrophilic nucleolar organizer regions (AgNOR), silver‐stained nucleolar organizer regions, were thought to reflect the cellular proliferative activity and the grade of malignancy. In liver diseases, it has been reported that AgNOR scores for hepatocellular carcinomas (HCC) were significantly higher than those for benign and borderline lesions; the scores increased with histologic tumor grade.

Autopsy case of primary choriocarcinoma of the urinary bladder.

Choriocarcinomas usually develop in the uterus and ovaries in the female, being extremely rare in the extragenital organs in the male. Extragenital choriocarcinomas in the male usually develop in the mediastinum or retroperitoneum. The frequency of choriocarcinoma in the urinary bladder is extremely low. The purpose of the present paper was to report an autopsy case of choriocarcinoma in the urinary bladder in the male. An 81‐year‐old male patient with macrohematuria was first diagnosed with transitional cell carcinoma (TCC). At autopsy a hemorrhagic necrotic tumor, which was found in the urinary bladder with metastatic lesions in the lungs, was diagnosed as choriocarcinoma microscopically. There was no evidence for choriocarcinoma derived from any other organs than the urinary bladder, although there were metastatic lesions in both lungs and the direct invasion into the prostate. From these findings it is concluded that the tumor was a primary choriocarcinoma in the urinary bladder in a male patient. Choriocarcinoma of the urinary bladder is very rare, but the prognosis is extremely poor in comparison with TCC even in the urinary bladder. Therefore, it is essential to clearly discriminate between choriocarcinomas and TCC.

Pulmonary infarction and deep venous thrombosis in a 13-year-old boy with Churg–Strauss syndrome

childhood, such as anaphylactoid purpura and Kawasaki disease, there are some rare but important disorders affecting children. Churg–Strauss syndrome (CSS) is one of these and is characterized by hypereosinophilia and systemic vasculitis that develops in patients with allergic disorders.1 Some patients with CSS have multisystemic involvement and often have various complications.2,3 The purpose of this report is to describe a case of CSS associated with pulmonary infarction and deep venous thrombosis and to summarize the patients in childhood previously reported.

A solitary fibrous tumor in the perianal region with a 13-year follow-up: Report of a case

A case of a solitary fibrous tumor (SFT) of the perianal region in a 62-year-old man is reported herein. The patient had undergone an abdominoperineal excision of the rectum for an anorectal tumor 13 years previously, and had been referred to our hospital for a perineal mass. Computerized tomography and angiography revealed a markedly hypervascular tumor measuring 11×8 cm in size in the pelvic cavity. After preoperative radiotherapy (total 58 Gy) and the embolization of the feeding arteries, he underwent an en bloc excision of the tumor. Microscopically, the tumor was composed of spindle shaped cells with a “patternless” arrangement in a collagenous background. There was immunohistochemical evidence that these cells were strongly positive for CD34, thus suggesting the tumor to be SFT. The previously resected anorectal tumor showed similar histological and immunohistochemical findings. The patient’s recovery was uneventful.