Masato Ohshima

K-ras activation and ras p21 expression in latent prostatic carcinoma in Japanese men.

Twenty‐three clinically silent prostatic carcinomas discovered in Japanese men at autopsy were surveyed for ras proto‐oncogene mutations by mutation‐specific oligonucleotide probe hybridization after polymerase chain reaction (PCR) amplification from a section of formalin‐fixed, paraffin‐embedded tissue. Six of the 22 that were satisfactorily amplified contained activating point mutations in codon 12 of K‐ras, a significantly higher frequency than has been reported in patients with clinically advanced disease in the United States. Of the six cases with activating point mutations in codon 12 of K‐ras, one had a GGT → GAT transition, four had GGT → GTT trans‐versions, and one had both GGT → GAT and GGT → GTT mutations. Sections from the same tissues were immunohistochemically stained with an anti‐ras p21 antibody. Carcinoma cells stained for ras p21 to some degree in 13 cases. Immunohistochemically detectable expression of p21 was always focal and was not necessarily associated with K‐ras mutation. K‐ras oncogene activation in prostatic carcinoma appears to merit additional study as a significant event in the pathogenesis of this neoplasm.

Immunohistochemical analysis of estrogen receptors in 313 paraffin section cases of human thyroid tissue

Three hundred and thirteen cases of human thyroid tissues, comprising 39 nodular goiters from 34 females and 5 males, 130 adenomas from 93 females and 37 males, and 144 carcinomas from 99 females and 45 males were used for the present immunohistochemical assessment of estrogen receptor (ER) expression. Thirty-three cases of follicular carcinoma, 115 cases of papillary carcinoma and 6 cases of anaplastic carcinoma were included in the malignant tumor group. Incidences of ER-positive cases were 23/39 (58.9%) for nodular goiter, 44/130 (33.8%) for adenoma and 26/144 (18.0%) for cancer. In the individual carcinoma categories, 7/23 (30.4%) follicular, 19/115 (16.5%) papillary and 0/6 (0%) anaplastic lesions were judged as positive cases. Thus, the incidence of ER-positive cases tended to decrease with the degree of malignancy; this trend being similar in both sexes. Moreover, the average ages of ER-positive cases were lower than those of ER-negative cases for all types of thyroid carcinoma except the follicular variety in males. It was thus suggested that ER expression may be related to prognosis and tumor growth at early stage. Since the incidence of ER does not significantly differ between females and males, the observed sex differences regarding thyroid tumor incidence may reflect the higher estrogen serum content in females.

Immunohistochemical evaluation of estrogen receptor status in benign prostatic hypertrophy and in prostate carcinoma and the relationship to efficacy of endocrine therapy.

The levels of estrogen receptors in human benign prostatic hypertrophy and in various pathological classifications of prostate carcinoma were assessed using immunohistochemical methods. All cases of benign hypertrophy showed elevated levels of estrogen receptor, while receptor-positive cells were detected in only 48% of carcinomas, indicating a negative correlation between receptor status and malignancy. Furthermore, the prognosis for effective endocrine therapy was poor in cases where tissues demonstrated low or negative receptor levels. In addition, the estrogen receptor status was compared to cell kinetic index such as proliferating cell nuclear antigen and argyrophilic staining of the nuclear organizer region.

Unsuspected gallbladder cancer diagnosed by laparoscopic cholecystectomy: A clinicopathological study

Laparoscopic cholecystectomy (LC) for gallstones has become a popular treatment modality, but LC for gallbladder cancer is not yet established and its prognosis is still unknown. We clinicopathologically studied unsupected gallbladder cancer presenting at pathologic evaluation after LC. The entire cross section of gallbladders after 456 LCs was histologically examined. The presence of malignant lesions was confirmed in 13 (2.85%) of 456 cases. The preoperative diagnoses were gallstones in 5 patients, gallbladder polyps in 5, gallstones with gallbladder polyps in 2, and gallstones with adenomyomatosis in 1. The carcinoma had invaded the mucosa in 7, the proper muscle in 2, and the subserosa in 3; the serosa was exposed in 1. The tumor size ranged from 2 mm to the entire gallbladder. An additional resection was performed in 2 patients. During the mean follow-up period of 25.9 months, 1 patient died of recurrence at 8 months while 1 demonstrated recurrence at the port site 1 year after surgery. No other patients have had any recurrence to date. Since early gallbladder cancer removed laparoscopically can be expected to have a satisfactory outcome, diagnostic and therapeutic LC is recommended in cases where total biopsy is indicate. However, in every case, extreme caution needs to be exercised to prevent the dissemination and implantation of cancer cells at the port site.

Expression of KAI1 in paraffin‐embedded normal, hyperplastic and neoplastic prostate and prostate carcinoma cell lines

Expression of KAI1, a tumor metastasis suppressor gene, was studied with different fixatives in frozen and paraffin‐embedded sections of human and rat prostate carcinoma cell lines and human prostate lesions by Immunohisto‐chemistry. Immunoreactivity of the membrane antigen in cell lines was associated with known expression levels in these lines and the fixative used. Formalin and paraformaldehyde helped maintain the immunoreactivity of cells. In human prostate, frozen sections revealed diffuse reactivity of the antigen in normal and neoplastic tissues while paraffin‐embedded tissues usually showed focal reactivity, although more than 50% of cases with normal epithelium and adenocarcinomas were reactive. In some cases, pretreatment with trypsln enhanced immunoreactivity. Benign prostatic hyperplasia (BPH) showed the most intense diffuse immunoreactivity, which suggested enhanced expression. Prostatic intraepithelial neoplasia (PIN) also often expressed high levels of KAI1. Three of five metastases were reactive but two primaries and their metastases were not. Lymphocytes in primary carcinomas and lymphocytes and germinal center cells in lymph nodes were immunoreactive, while adjacent primary or metastatic prostate adenocarcinoma epithelium was not immunoreactive. Although paraffin‐embedded human tissues were not optimal for determining levels of expression of KAI1, they did show immunoreactivity that could have prognostic value and showed the specific cytoplasmlc localization of the protein in cells.

Immunohistochemical Detection of Estrogen Receptors in Paraffin Sections of Human Thyroid Tissues

The optimal demonstration of estrogen receptor binding in thyroid tissues was made under conditions of 10% protease in 50 mM Tris-HCl buffer (pH 7.6) for 10 min as the pretreatment digestion step, incubation of primary antibody (ER-ICA monoclonal kit; Abbott Laboratories) at 37 degrees C for 2 h and incubation of secondary antibody (ABC kit; Vector) at 37 degrees C for 40 min. Thyroid tissues used for assessing the reaction were 17 cases of goiter, 25 adenoma cases, 27 cases of papillary carcinoma, 14 cases of follicular carcinoma and 10 latent cancer cases. Incidences of positive estrogen receptor reaction were 22% (11/51) for all thyroid cancers, 20% (5/25) for the thyroid adenomas and 59% (10/17) for goiters. 15% (4/27) of papillary carcinomas, 21% (3/14) of follicular carcinomas and 40% (4/10) of latent cancers proved positive, the estrogen receptor reaction being limited to the nuclei of thyroid follicular/papillary type cells.

Three‐Dimensional Observations By Scanning Electron Microscopy on the Blood Supply and Organization of Vasculature During Hepatocarcinogenesis in Rats

Three‐dimensional vascular changes in rats during hepatocarcinogenesis were studied by stereoscopic and scanning electron microscopic observation of vascular casts of sinusoids by injecting resin from hepatic artery (red color) and portal vein (blue color). Neoplastic lesions were synchronously induced by injection of diethylnitrosamine (DENA) followed by feeding of 2‐acetylaminofluorene (2‐AAF) plus partial hepatectomy, then periodically killed for examination. At 6 weeks after DENA injection sinusoids of hyperplastic foci (HF) were filled with blue resin similar to surrounding tissue, then at 8 weeks some HF and hyperplastic nodules (HN) took up red resin leaving surrounding sinusoids blue. At 12 to 18 weeks, red HN became more discrete with obvious compression of surroundings but decreased their number whereas blue HN were not. Red HN had incomplete anastomosing sinusoids giving a coral‐like appearance. Spongy or cystic areas contained little or no resin, suggesting ischemic condition. Hepatocellular carcinomas (HCC) at 40 weeks took exclusively arterial red resin forming irregularly shaped anastomosing sinusoids. These findings indicate that acquisition of arterial blood supply by HF may relate to their further development to persistent HN and HCC.

Primary plasmacytoma of the thyroid: A case report and comparative literature study between Western nations and Japan

A 52 year old man presented with primary thyroid plasmacytoma. The patient was initially followed up for thyroid dysfunction. The histological examination of the removed thyroid revealed a proliferation of mature and immature plasma cells indicative of plasmacytoma with Hashimotos disease. After radiotherapy (40 Gy) to the neck following right hemi‐thyroidectomy, the patient is currently alive and well 3 years after diagnosis without any evidence of tumor. The immunohistological examination of the removed thyroid showed monoclonality for immunoglobulin G‐Kapa light chains. Sixty‐six literature cases of primary thyroid plasmacytoma were reviewed and comparison of the clinical and histological characteristics between Japanese and Western cases noted. The incidence of the patients with antithyroid antibody was significantly lower (P < 0.01) in Western patients (42.9%) than in Japanese patients (87.5%). The higher incidence of thyroid dysfunction and Hashimotos disease in Japan in comparison with Western nations was well reflected in the incidence of antithyroid antibody.

A Resected Case of Carcinoma of the Pancreatic Tail Presenting as Jejunal Ileus

症例は72 歳の男性で, 56歳時に胃癌で胃全摘および脾摘を受けている. 上腹部痛を主訴に当科を受診し, イレウスと診断した. イレウス管からの造影で空腸に閉塞を認め, 癒着性イレウスを疑って開腹術を施行した. 径5cm大の膵尾部腫瘍が横行結腸間膜を超えて空腸に直接浸潤していた. 膵体尾部・左副腎合併切除, 空腸部分切除, 横行結腸部分切除を施行した. 病理組織学的には膵尾部の中分化型管状腺癌で, 空腸と左副腎に直接浸潤し, 進行度はstage IVaであった. 術後3 か月目に傍大動脈リンパ節再発を認め, gemcitabineによる全身化学療法を施行中で, 術後13か月目の現在生存中である. イレウスで発症した膵癌は本邦では自験例を含め10例のみの報告で, 空腸イレウスで発症したのは自験例のみであった. 小腸イレウスの原因疾患として, 膵癌も鑑別診断の1つとして考慮すべきと考えられた.