Search PubMed⌕ Search

Biomedical subjects

S G Silverberg

Publications and source records attributed to S G Silverberg.

At least 73 records · Page 4Linked to original sources

Association of endometrial epithelial metaplasias with endometrial carcinoma and hyperplasia in Japanese and American women.

We reviewed endometrial tissue from 166 cases of endometrial adenocarcinoma and hyperplasia--91 seen at Kyushu University, Fukuoka, Japan, and 75 at George Washington University, Washington, D.C., U.S.A.--to compare the prevalence of epithelial metaplastic changes in the two populations. Metaplasias were more common in the benign endometrium associated with carcinoma at George Washington University (78%) than at Kyushu University (54%). They were associated with carcinomas of lower grade and accompanied by hyperplasia at both institutions. These results indicate that endometrial metaplasias, like endometrial hyperplasias, tend to be associated with less virulent endometrial carcinomas and to be more common in American women (who represent a high-risk population for endometrial carcinoma) than in Japanese women (in whom the risk is low but rising.

Endometrial Hyperplasia↗

Clinical implications of K-ras mutations in malignant epithelial tumors of the endometrium.

Tumorigenesis in humans and experimental animals appears to involve the activation of ras protooncogenes for a number of organ systems and seems to be important to the development of the metastatic phenotype in several model systems. Clinically, the presence of activated ras protooncogenes has been reported to be a negative prognostic factor in the myelodysplastic syndrome and in adenocarcinoma of the lung. In the present study we examined 49 cases of endometrial carcinoma for mutations in the first exon of K-ras using the polymerase chain reaction and direct sequencing. Mutations in codon 12 or 13 of K-ras were detected in 6 of 49 cases (12.2%). These six cases consisted of five endometrioid endometrial carcinomas, each of which had a mutation in codon 12, and one case of clear cell carcinoma, which had a mutation in codon 13. In our study the presence of mutations in K-ras appeared to be an unfavorable prognostic factor. Three of six patients with the mutation died during follow-up, while only 7% of the 43 patients without K-ras mutations expired during this same period. In multivariate analysis using the Cox proportional hazard model, K-ras activation appeared to be an independent risk factor when compared with clinical stage, depth of myometrial invasion, and patient age. Thus, our findings support the hypothesis that K-ras protooncogene activation plays an important role in determining the aggressiveness of endometrial carcinoma.

Base Sequence↗

Should we report cervical smears lacking endocervical component as unsatisfactory?

The purpose of the study is to correlate the accuracy of diagnosis of cervical smears with the presence/absence of an endocervical component. The referral smears and the smears obtained during colposcopic examination of 84 patients with biopsy-proven squamous lesions were evaluated for the presence of an endocervical component, and the cytologic interpretations were compared with the histologic findings. Of the 136 smears containing an endocervical component, 111 (81.6 percent) had good correlation with histology and 25 (18.4%) showed a discrepancy. Of the 30 smears lacking an endocervical component, 24 (80%) had good histologic correlation and 6 (20%) were discrepant. Our data showed no significant difference in the detection of squamous lesions in those smears with an endocervical component from those without. We conclude that, although the presence or absence of an endocervical component should be documented in the cytology report, its absence should not be an indication to report the cervical smears as unsatisfactory.

Adolescent↗

Immunolocalization of c-myc oncoprotein in mucinous and serous adenocarcinomas of the ovary.

Activation of c-myc oncogene has been reported in increasing numbers of human ovarian carcinomas and appears to play a role in the biologic behavior of the neoplasms. We have studied the immunohistochemical localization of p-62c-myc, the gene product of c-myc, in 44 cases of serous and mucinous cystadenoma, adenocarcinoma of low malignant potential, and invasive adenocarcinoma, using a monoclonal antibody raised to a synthetic human p62c-myc sequence (Myc 1-6E10). Both serous and mucinous cystadenomas demonstrated a higher frequency of nuclear localization than did carcinomas, which showed much greater cytoplasmic staining, while tumors of low malignant potential showed an intermediate pattern. However, the observed differences did not reach statistical significance. No significant correlation was observed between intracellular localization patterns of p62c-myc and histologic and nuclear grades and mitotic activity in the cases of carcinoma. Great care should be taken in the interpretation of immunohistochemical analysis of oncogene products, especially when attempting to correlate the findings with biologic tumor behavior.

Adenocarcinoma, Mucinous↗

Immunolocalization of epidermal growth factor receptor and c-erbB-2 oncogene product in human ovarian carcinoma.

Abnormalities of epidermal growth factor receptor (EGFR) and c-erbB-2 have been demonstrated to be correlated with aggressive biologic behavior in a variety of human cancers. To analyze the possible roles of these oncogenes in ovarian neoplasms, immunolocalization of EGFR and c-erbB-2 oncogene product was performed in 45 cases of human ovarian mucinous and serous cystadenomas, carcinomas of low malignant potential (LMP), and invasive carcinomas by employing antibodies against these oncogene products. EGFR immunoreactivity was present in 15 of 35 LMP and invasive carcinomas and 1 of 10 cystadenomas. On the contrary, immunoreactivity of p185, which is an oncogene product of c-erbB-2, was detected only in five cases of carcinoma and in no benign cystadenoma. These results indicate that EGFR may be involved in the neoplastic process in epithelial ovarian adenocarcinoma, especially mucinous carcinoma, but involvement of c-erbB-2 is probably not as prevalent as considered previously. Four of the five cases immunohistochemically positive for p185 were also positive for EGFR, which suggests that expression of EGFR and p185 is to some extent correlated in human ovarian carcinoma.

Biomarkers, Tumor↗

Adenosarcoma of the uterus: a Gynecologic Oncology Group clinicopathologic study of 31 cases.

We report on the clinical and pathologic findings in 31 cases of adenosarcoma of the uterus subjected to hysterectomy and staging laparotomy. Nine of 30 patients (30%) have had recurrent tumor and six of 30 (20%) have already died of tumor in a relatively short follow-up period (mean, 38.3 months). Seventeen of 31 cases were diagnosed as adenosarcoma with sarcomatous overgrowth (SO). Ten of these 17 with SO contained focal or extensive rhabdomyosarcoma. In six cases, extrauterine spread was identified as follows (two patients had two sites each): vaginal involvement (two cases), pelvic lymph node metastases (two), positive peritoneal cytologic findings (two), parametrial invasion (one), and ovarian metastasis (one). Extrauterine spread (stage III) (p less than 0.001) and myometrial invasion (p = 0.04) were associated with higher rates of recurrence. The presence of lymphatic and/or vascular invasion, SO, and rhabdomyosarcomatous differentiation also indicated poor prognosis but did not attain statistical significance. Based on this experience, staging laparotomy including peritoneal cytology is suggested in cases of clinical stages I and II adenosarcoma. The differential diagnosis of these tumors is also discussed.

Adult↗

Lectin histochemistry in mucinous and serous ovarian neoplasms.

The lectin-binding properties of 44 cases of serous and mucinous ovarian cystadenoma, tumor of low malignant potential (LMP), and invasive carcinoma were examined histochemically. Wheat germ agglutinin (WGA), concanavalin A (con A), Ulex europaeus agglutinin I (UEA-I), peanut agglutinin (PNA), Ricinus communis agglutinin I (RCA-I), soybean agglutinin (SBA), and Robina pseudoaccacia (RPA) were employed. All the lectins examined were bound to neoplastic epithelial cells of benign and malignant tumors, but none bound exclusively to ovarian tumor cells. Different lectin-binding patterns between serous and mucinous neoplasms were observed, with the exception of RPA. UEA-I, con A, RPA, and PNA in serous neoplasms and UEA-I, RPA, and WGA in mucinous neoplasms demonstrated lectin-binding properties of LMP tumors intermediate between those of cystadenoma and invasive carcinoma. These findings indicate that serous and mucinous ovarian neoplasms contain different glycoconjugates, that malignant transformation of the neoplasms is associated with alteration of these glycoconjugates, and especially that LMP tumors have a different composition of cellular glycoconjugates from that of invasive ovarian carcinoma.

Adenocarcinoma, Mucinous↗

Human papilloma virus in uterine cervix: a comparison of detection by morphology and by dot-blot hybridization.

Colposcopically directed cervical biopsies, smears, and swabs obtained from 210 women with a previous abnormal cervical cytology were evaluated for the presence of human papilloma virus (HPV) using morphology and dot-blot hybridization. The diagnosis of HPV infection in biopsies and smears examined morphologically was rendered using established criteria for condyloma/cervical intraepithelial neoplasia (CIN). In hybridization studies, DNA was isolated from cells obtained from cervical swabs and annealed with probes that detected HPV types 6/11, 16/18, and 31/33/35 using a dot-blot procedure. Ninety-five cases demonstrated morphologic evidence of condyloma/CIN; 51 of these (54%) were positive for HPV DNA (five cases 6/11, 21 cases 6/18, 20 cases 31/33/35, and five cases two different probes). HPV DNA was also detected in 6 of the 115 cases (5.2%) that were morphologically negative (three cases 16/18, three cases 31/33/35). The results demonstrated that morphology was more sensitive than dot-blot hybridization for detection of HPV-related lesions. The dot-blot hybridization did detect HPV DNA in a small percentage of the cases that showed no morphologic abnormality and was useful for typing of the HPV. At this juncture, however, the clinical significance of the latter findings is unclear.

Cervix Uteri↗

Hyaline globules in Kaposi's sarcoma: a light microscopic and immunohistochemical study.

Hyaline globules (HG) were detected in 51 of 54 Kaposi's sarcoma (KS) lesions (94.4%), including all four non-acquired immunodeficiency syndrome (AIDS) cases of cutaneous KS in this group of cases. Thus, there was no correlation between the presence of HG and the presence or absence of AIDS, nor could we demonstrate any relationship between the presence or prominence of HG and either the histologic pattern or anatomical distribution of KS. HG were located mainly in the cytoplasm of perivascular cells, histiocytoid cells, and spindle-shaped cells and occasionally in endothelial cells lining vessels or slit-like spaces. Extracellular HG were also seen. HG stained positively with periodic acid-Schiff with and without diastase digestion and with phosphotungstic acid-hematoxylin. HG were immunohistochemically negative for alpha 1-antitrypsin, alpha 1-antichymotrypsin, lysozyme, and Factor VIII-related antigen, but the cells containing HG were often positive for alpha 1-antichymotrypsin and occasionally for alpha 1-antitrypsin and Factor VIII-related antigen. HG were also detected in five of six angiosarcomas, two of ten pyogenic granulomas, and seven of 32 inflammatory granulation tissues. These were immunohistochemically similar to HG in KS. Thus, HG are not specific for KS. We support the interpretation that HG are most likely digested erythrocytes.

Acquired Immunodeficiency Syndrome↗

An analysis of abnormalities of the retinoblastoma gene in human ovarian and endometrial carcinoma.

The altered expression of the human retinoblastoma (RB) gene has been demonstrated to play an important role in the pathogenesis of RB and other tumors. To determine whether the RB gene might be involved in the pathogenesis of human ovarian and endometrial cancer, DNA from 24 human ovarian tumors, 3 normal ovaries, 3 endometrial carcinomas, and 1 endometrial hyperplasia was examined with an RB complementary DNA probe. Evidence for homozygous deletion of the RB gene was observed in only one specimen. Interestingly, the specimen was an endometrioid tumor of the ovary of low malignant potential (LMP). This patient experienced rapid progression of the tumor and died 8 months after diagnosis. Abnormalities of the RB gene may be involved in the aggressive biologic behavior of certain forms of ovarian carcinoma, particularly those of LMP.

Aged↗

Kaposi's sarcoma in patients with acquired immune deficiency syndrome. A flow cytometric DNA analysis of 26 lesions in 21 patients.

The DNA content of formalin-fixed, paraffin-embedded tissue from 21 patients (26 lesions) with Kaposi's sarcoma associated with acquired immune deficiency syndrome (AIDS) was analyzed by flow cytometry. The lesions were classified histologically into the following three types according to the predominant pattern: granulation tissue-like (two lesions), angioma/angiosarcoma-like (ten lesions), and spindle cell (14 lesions). All lesions showed exclusively DNA diploidy, and the S- phase fractions were usually low, ranging from 2% to 13% (mean, 6.9%). The follow-up periods were from 2 to 60 months. Five patients died, with one of the deaths attributed to pulmonary failure resulting from diffuse alveolar damage and Kaposi's sarcoma; the other deaths were attributed to infections. These results indicate that Kaposi's sarcoma is not a high-grade neoplasm and, combined with previously reported evidence, may suggest that Kaposi's sarcoma associated with AIDS is a proliferative process rather than a malignant neoplasm.

Acquired Immunodeficiency Syndrome↗

Infiltrating cribriform carcinoma of the breast: a distinctive clinicopathologic entity.

All cases of primary breast carcinoma seen at the George Washington University Medical Center between 1971 and 1975 and between 1981 and 1986 were reviewed, and examples of pure and mixed infiltrating cribriform carcinoma (ICC) were identified. The relative frequency of ICC did not change significantly from the earlier to the later study period. As previously reported by Page et al, there was a tendency for ICC to be associated with foci of tubular carcinoma and of intraductal carcinoma (often but not always of cribriform type). Pure ICC (defined as showing no other infiltrating carcinoma type), predominant ICC with lesser amounts of infiltrating carcinoma of any other type and any quantitative combination of ICC and tubular carcinoma metastasized to axillary lymph nodes frequently, but almost never to more than three nodes, in contradistinction to tumors composed of infiltrating duct carcinoma (IDC) not otherwise specified and less than 50% ICC, and a control group of IDC, which significantly more often involved four or more nodes. ICC cases were estrogen-receptor-positive in 100% and progesterone-receptor-positive in 69% of the cases. Five-year survival rates for eligible cases were 100% for pure and greater than or equal to 50% ICC, 88% for less than 50% ICC, and 78.3% for the IDC controls. ICC is a histologically and clinically distinctive type of mammary carcinoma that should be separated from IDC and other tumor types.

Adenocarcinoma↗

Carcinosarcoma (malignant mixed mesodermal tumor) of the uterus. A Gynecologic Oncology Group pathologic study of 203 cases.

We report on the pathologic findings in primary tumors and metastases in 203 cases of stage I and II endometrial carcinosarcoma (malignant mixed mesodermal tumor) subjected to hysterectomy and staging laparotomy. Metastases were studied in 40 of these cases, including 34 with positive findings in the pelvic and/or para-aortic lymph nodes. Features of the stromal component of the primary tumors, including grade, mitotic index, and the presence and types of heterologous elements, showed no relation to the presence of metastases at operation. High-grade, serous, and clear cell carcinomatous components, on the other hand, were associated with a higher frequency of metastases, as were deep myometrial invasion, lymphatic or vascular space invasion, and involvement of the isthmus or cervix. The current concepts of histogenesis and differentiation of these tumors are discussed, and the suggestion is made that they might represent metaplastic carcinomas.

Carcinosarcoma↗