Two cases of pancreatic tumor consisting of duct, acinar, and islet components are reported. Both tumors measured about 1.0 cm in diameter and were without definite fibrous encapsulation. Histologic, immunocytochemical, and electron microscopic studies revealed three distinct cell populations: duct, acinar, and islet cells. Both endocrine and exocrine components were seen within the same cell nest. Islet components predominated in both cases. Nearly all the cells in the islet component were positive for insulin. Few cells positive for glucagon, somatostatin, or pancreatic polypeptide were present within the tumor cell nests. Duct cells were the least conspicuous cellular element of the tumor; they were positive for mucin and immunoreactive for cytokeratin and carcinoembryonic antigens (CEA). The acinar component was the minor element of the tumor in both cases. Electron microscopic study also confirmed three different cell populations in the tumor: duct cells arranged in a ductal structure with intercellular attachments and microvilli, islet cells containing beta granules, and acinar cells with zymogen granules. The tumors presented herein indicate that both their endocrine and exocrine components might have been derived from a common precursor. The implication and significance of the differentiation of different cells within the same tumor is discussed in relation to the concept of an amine precursor uptake and decarboxylation (APUD) system.

Adenoma, Islet Cell↗

PubMedDate not supplied

Metanephric adenoma of the kidney: an electron microscopic and immunohistochemical study with quantitative DNA measurement by image analysis.

Metanephric adenoma of the kidney is a newly recognized entity of renal adenoma, and the electron microscopic and immunohistochemical features of the tumor have not yet been well elucidated. The authors experienced a typical case of renal metanephric adenoma and studied the electron microscopic and immunohistochemical features of the tumor together with the DNA content of the tumor cells. Electron microscopically, the tumor was composed of immature epithelial cells with relatively uniform size, poor nuclear polarity, and scant cytoplasmic organelles arranged in small tubular or rosette pattern. Immunohistochemically, the cytoplasm of the majority of the tumor cells was positive for S-100, and occasionally for alpha-1-antitrypsin and vimentin. The tumor cells were also positive for cytokeratin, lysozyme, and Leu 7, with predominantly cell membrane staining. Only tumor cells arranged in papillary or large tubular pattern were positive for epithelial membrane antigen (EMA). Tumor cells were negative for Leu M1 and HMB-45. These immunohistochemical characteristics are quite similar to those of S-shaped body of the fetal kidney. An analysis of the nuclear DNA of the tumor cells by image cytometry revealed that the tumor entirely consisted of diploid cells' and lacked aneuploid cells. These results indicate that renal metanephric adenoma is composed of immature renal epithelial cells.

Adenoma↗

PubMedDate not supplied

Epithelial hyperplasia of the gallbladder in children with anomalous pancreaticobiliary ductal union.

BACKGROUND/AIMS: Few data are available on the fate and incidence of epithelial hyperplasia throughout the life of anomalous pancreaticobiliary ductal union (APBD) patients. The pathological study in pediatric APBD patients is less recognized. METHODOLOGY: Ten resected gallbladders obtained from children with APBD and control patients without APBD were examined histologically, and immunohistochemically for the detection of Ki-67 (as a proliferative marker) and p53. K-ras mutations in codon 12 were also examined. Epithelial hyperplasia was classified into high-grade and low-grade hyperplasia. RESULTS: Six (60%) of 10 patients with APBD had epithelial hyperplasia of the gallbladder, whereas no patients without APBD exhibited this lesion. Diffuse epithelial hyperplasia was observed in 1 (50%) of 2 undilated-type APBD and 5 (63%) of 8 dilated-type. Two (33%) of 6 patients with epithelial hyperplasia exhibited high-grade hyperplasia. Ki-67 labeling index (LI) was significantly higher in hyperplastic mucosa than in control gallbladder mucosa. K-ras mutations and p53 overexpression were not detected in hyperplastic and normal mucosa. CONCLUSIONS: Epithelial hyperplasia of the gallbladder accompanied by increased proliferative activity exists at birth or is acquired in childhood with APBD patients and may be an important factor predisposing to the development of gallbladder carcinoma.

Cell Division↗

PubMedDate not supplied

Flow cytometric DNA measurement in benign and malignant human thyroid tissues.

The occurrence of aneuploidy in 108 normal, benign and malignant thyroid tissues was evaluated by DNA flow cytometry. Aneuploid cell populations were found in 60% of the papillary carcinomas, 67% of the follicular carcinomas, 52% of the follicular adenomas and in 10% of the multinodular goiters. None of the non-neoplastic thyroid lesions (chronic thyroiditis and Graves' disease) showed aneuploidy. No significant differences in frequency of aneuploidy and DNA index were found between the well-differentiated and trabecular types of the papillary carcinomas (53%; 1.29 +/- 0.10 vs 75%; 1.30 +/- 0.10, respectively), although the latter type of papillary carcinomas have been shown to be associated with a more aggressive clinical behavior. Also no differences in frequency of aneuploidy were noted between the follicular carcinomas and the follicular adenomas, but the DNA index was significantly higher in the former. These findings indicate that flow cytometric analysis of DNA content may not be helpful in the evaluation of the clinical behavior of papillary carcinomas or in the determination of malignancy of follicular tumors, but may be useful in differentiating neoplastic from non-neoplastic thyroid lesions.

Adenocarcinoma↗

PubMedDate not supplied

Immunohistochemical study of oncogene product ras p21, c-myc and growth factor EGF in breast carcinomas.

The expression of the oncogene products ras p21, c-myc and the growth factor EGF (epidermal growth factor) was studied immunohistochemically in the tissue of 119 benign and malignant human breasts. In most cases, histologically normal breast tissues and benign lesions were found to be negative or poorly-expressive for reactivity with each antibody. Similar findings were observed in carcinoma in situ. Invading breast carcinomas demonstrated a significantly higher percentage of stained cells than that observed in benign lesions or carcinoma in situ; forty-two of 66 invasive breast carcinomas (63.6%) were highly-expressive for ras p21, thirty-eight (57.6%) for c-myc and twenty (30.3%) for EGF, but overall correlations between each oncogene expression and the clinical stage, tumor size or degree of differentiation were not found. The overall 5-year survival rate was studied in 58 patients with Stage II and III in association with each oncogene or EGF expression. Their survival rate was significantly effected by the EGF expression (0.05 less than p less than 0.1) but not by ras p21 or c-myc expression. Analysis of 36 specimens available with ER (estrogen-receptor) level revealed a significant correlation between the ER status and c-myc or E2 (estradiol) and a significant inverse correlation between ER status and ras p21 or EGF expression (P less than 0.05). The expression of ras p21, EGF and c-myc was not associated with metastatic tumor progression.

Antibodies↗

PubMedDate not supplied

The relation of argyrophilic proteins of nucleolar organizer regions (AgNORs) to the proportions of Ki-67 or DNA polymerase alpha-reacting cells in non-Hodgkin's lymphomas.

In order to examine the relationship between argyrophilic proteins of nucleolar organizer regions (AgNORs) and the proliferation activity of cells, we investigated lymph nodes obtained from 25 untreated non-Hodgkin's lymphoma (NHL) patients. Two monoclonal antibodies (MoAb) (Ki-67 antibody and anti-DNA polymerase alpha antibody) were used for evaluating cell proliferation activity. A linear relation between the mean number of agNORs per nucleus and the proportion of NHL cells reacting with Ki-67 MoAb was observed (r = 0.48, P less than 0.05). A similar relation between AgNORs and DNA polymerase alpha MoAb was also observed (r = 0.51, P less than 0.01). From these data, it was confirmed that AgNORs reflect the proliferation activity of NHL cells. We conclude that the AgNOR staining procedure is one of the simplest and most reliable methods for analyzing cell proliferation potential.

Antibodies, Monoclonal↗

PubMedDate not supplied

Effects of tamoxifen, medroxyprogesterone acetate and estradiol on tumor growth and oncogene expression in MCF-7 breast cancer cell line transplanted into nude mice.

The effects of three hormonal agents with a different mechanism of action (tamoxifen [TAM], medroxyprogesterone acetate [MPA] and estradiol [E2]) on tumor growth, differentiation and oncogene expression were evaluated using the estrogen-receptor positive human breast carcinoma cell line MCF-7 transplanted into nude mice. In MCF-7 tumors treated with E2, tumor incidence, mean weight of tumors, 3H-thymidine labelling index, differentiation antigen HMFGM (human milk-fat globule membrane) and ras p21, c-myc, neu oncogene products, the level was significantly increased. On the other hand MPA suppressed all of them. TAM increased the level of c-myc expression and HMFGM antigen, but suppressed the others. This evidence indicates that E2 induces both proliferation and differentiation of MCF-7 tumor cells. MPA suppresses both proliferation and differentiation, and TAM induces differentiation and suppresses proliferation.

Animals↗

PubMedDate not supplied

Immunohistochemical demonstration of growth factors, TGF-alpha, TGF-beta, IGF-I and neu oncogene product in benign and malignant human breast tissues.

The expression of growth factors, TGF-alpha, TGF-beta, IGF-I and neu oncogene product was studied immunohistochemically in the tissue of 120 benign and malignant human breasts. Growth factors were found only in benign or malignant mammary epithelial cells and not in stromal cells. Normal and benign lesions were found to be negative for reactivity with each antibody. Carcinoma in situ and invasive breast carcinomas demonstrated a significantly higher percentage of stained cells than that observed in benign lesions; forty (49%) of 82 invasive carcinomas were positive for TGF-alpha, 31 (38%) for TGF-beta, 31 (38%) for IGF-I and 34 (41%) for neu product. No overall correlations were found between expression of each growth factor and the clinical stage or degree of histologic differentiation of the carcinomas. A significant positive correlation was observed between ER status and IGF-I expression and between PgR status and TGF-beta expression. In the majority of the carcinomas, co-expression between TGF-alpha, TGF-beta and IGF-I was observed; the percentage of cases with parallel positive or negative expression of two growth factors was as follows; TGF-alpha - TGF-beta (70%), TGF-alpha - IGF-I (57%), TGF-beta - IGF-I (71%). The concomitant expression of TGF-alpha and neu oncogene product in cell surface was also observed. The relapse-free intervals of the patients were studied in association with expression of each growth factor. TGF-beta-positive tumors showed a significantly better prognosis than TGF-beta - negative tumors (within the first 2 years of observation). However, TGF-alpha, IGF-I and neu overexpression showed no effect on the prognosis of the patients.

Adult↗