Re: Endometrial cancer in tamoxifen-treated breast cancer patients: findings from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14.
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Breast Neoplasms↗
Biomedical subjects
M L Carcangiu
Publications and source records attributed to M L Carcangiu.
Numerical chromosomal aberrations in thyroid tumors detected by double fluorescence in situ hybridization.
Double fluorescence in situ hybridization with DNA probes specific for the (peri)centromeric regions of chromosomes 3, 7, 9, 11, 12, 18, and X was performed on fresh isolated nuclei and frozen tissue sections prepared from 2 nodular hyperplasias, 2 adenomas, and 7 papillary carcinomas of the thyroid in order to detect numerical chromosomal changes. Numerical chromosomal aberrations were found in all malignant specimens examined. A consistent presence of at least two trisomies was detected in most cases, especially in the follicular variant specimens; the highest degree of trisomy was observed for chromosome 12. Isolated monosomies of moderate degree for different chromosomes were found in 1 adenoma and 2 papillary carcinomas. Severe monosomy of chromosome 9 was the only significant feature observed in the single metastatic papillary carcinoma.
Adult↗
Ovarian serous borderline tumors with lymph node involvement. Clinicopathologic and DNA content study of seven cases and review of the literature.
Although several studies have established the excellent prognosis of ovarian serous borderline tumors (OSBTs) in general, the significance of lymph node involvement has not been thoroughly addressed. In this article, we describe seven OSBTs with lymph node involvement and their DNA content and S-phase fraction. Lymph node involvement was identified at presentation in four cases (pelvic, paraaortic, and omental) and after 4, 5, and 7 years in the other three (omental, scalene, and cervical, respectively). In the first group, clusters of cells cytologically similar to those of the OSBT were identified in the nodal sinusoids in all four cases and focally in the lymph node parenchyma in three of them. In contrast, the involved lymph nodes of the three cases with delayed nodal disease showed an almost complete replacement by tumor. In one of them, the tumor in the lymph node was histologically similar to the OSBT, while in the other two cases the tumor was more solid and poorly differentiated, suggesting true metastatic disease. Flow cytometric analysis of nuclear DNA content and S-phase fraction were performed on paraffin-embedded tissue of all of the primary OSBTs and of the involved lymph nodes in six cases; diploid DNA content and low S-phase fraction were seen in all cases. All patients were alive and free of disease 2-9 years after initial diagnosis. While the clinical significance of LN involvement in OSBT is still uncertain, DNA ploidy analysis seems to be unable to identify those cases at risk for tumor progression.
Adolescent↗
Evaluation of leuprolide acetate treatment on histopathology of uterine myomata.
OBJECTIVE: To determine if short-term, preoperative leuprolide acetate (LA) therapy alters the histologic appearance of uterine leiomyomata. DESIGN: Retrospective evaluation by a pathologist (who was blinded to patient history) of the histologic features of leiomyomata excised from 36 women, 12 who received preoperative LA and 24 age-matched controls. SETTING: Yale-New Haven Hospital, New Haven, Connecticut, from September 1989 to September 1990. MAIN OUTCOME MEASURE: The histologic specimens were evaluated for the presence of mitotic activity, cellular atypia, cellularity, and secondary changes including edema, fibrosis, calcification, hemorrhage, infarction, hyalinization, and vascular appearance. RESULTS: Of the 12 patients treated with LA, 10 (84%) demonstrated a reduction in uterine volume after 3 to 6 months of LA therapy. There was no difference in any of the histopathologic parameters evaluated between the LA-treated group and the untreated group. Exclusion of leiomyoma, which did not have a reduction in size during LA therapy, did not alter the analysis. Among patients treated with LA, those leiomyoma that did not respond to LA had a greater degree of hyalinization than those that responded. CONCLUSION: Reduction in uterine size by short-term LA therapy did not detectably alter histologic appearance of leiomyoma.
Adult↗
Allelic loss in ovarian cancer.
Loss of heterozygosity (LOH) was examined at 86 loci distributed on every chromosomal arm in 50 human ovarian tumors. Frequent allele losses were observed on chromosomes 13q (42%), 17p (42%), 17q (45%), and Xp (41%). Deletion mapping on chromosome 17 revealed a candidate gene on the long arm distal to D17S41/S74 for ovarian cancer which is distant from the locus for early onset breast cancer. LOH on chromosome 17q was found to be concordant with LOH on chromosomes 3p, 13q, 17p and Xp suggesting that it may be an early event in neoplastic development. These findings indicate that multiple tumor-suppressor genes for ovarian cancer possibly exist on chromosomes 13q, 17, and/or Xp and provide the basis for the identification of candidate gene(s) associated with ovarian cancer. The chromosomal mechanisms resulting in allele losses in ovarian cancer include deletion, deletion/duplication, mitotic recombination and monosomy, in concordance with the developed genetic model.
Alleles↗
The ovarian renin-angiotensin system in polycystic ovarian syndrome.
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Animals↗
Advanced ovarian carcinoma: molecular evidence of unifocal origin.
The clonal origin has sometimes been disputed in advanced epithelial cancers when multiple sites of peritoneal tumors were present because of the developmental similarity of the surface epithelium of the ovary and the peritoneal mesothelium. We have taken two independent approaches to study the clonality of advanced epithelial carcinoma. Tumor samples of both ovaries, and/or omentum, and/or peritoneum from nine patients were examined. The analysis of loss of heterozygosity (LOH) at 86 polymorphic chromosomal loci distributed on every chromosome revealed the loss of the same allele in every tumor of each patient when LOH was detected. In addition, we used a restriction-fragment-length polymorphism in an X-linked sequence (DXS255) to examine the pattern of X-chromosome inactivation based on the differential methylation of DXS255 in active and inactive X chromosomes. Inactivation of the same X chromosome in various tumors from the same patient was observed in each of the five informative patients. Our results strongly suggest that the advanced epithelial cancers are monoclonal in origin.
Adult↗
Intravenous cisplatin, doxorubicin, and cyclophosphamide in the treatment of uterine papillary serous carcinoma (UPSC).
Thirty patients with uterine papillary serous carcinoma were treated with intravenous cisplatin, doxorubicin, and cyclophosphamide (CAP) chemotherapy, a combination with proven efficacy against ovarian carcinoma. Nineteen patients were given CAP as an adjuvant soon after surgery. Eleven patients were treated after recurrence or failure of other first-line therapy. Of the patients treated adjuvantly, 11 (58%) were alive without evidence of disease with a median follow-up of 24 months. Eight patients (42%), all with metastatic disease at diagnosis, were dead of disease (DOD) with a median survival of 14 months. In the salvage group, all patients were DOD with a median survival of 21 months from diagnosis and a median survival from initiation of CAP of 7 months. Toxicity was observed in all patients, and there was one treatment-related death from cardiotoxicity. In the salvage group there were two partial responses and one complete response (response rate = 27%). We conclude that intravenous CAP was ineffective in the treatment of metastatic or recurrent uterine papillary serious carcinoma, but deserves study as an adjuvant in patients without metastatic or with only microscopic extrauterine disease.
Aged↗
Colony-stimulating factor-1 in primary ascites of ovarian cancer is a significant predictor of survival.
OBJECTIVE: Our purpose was to determine whether the concentration of colony-stimulating factor in ascites of ovarian carcinoma is a prognostic factor for survival. STUDY DESIGN: Forty-four ascites samples from patients undergoing primary surgery for ovarian carcinoma were measured for colony-stimulating factor-1 by radioimmunoassay. Retrospective analysis of clinical data allowed comparison of accepted prognostic factors to ascites colony-stimulating factor-1 concentration for impact on survival by means of life-table analysis (Kaplan-Meier) by the Wilcoxon test and the Cox regression methods. RESULTS: In patients with advanced disease (International Federation of Gynecology and Obstetrics stages III and IV, n = 37) ascites colony-stimulating factor-1 concentration levels below a critical cutoff of 8.59 ng/ml were associated with longer overall survival (p < 0.05) and were a better predictor of survival than any other prognostic factor except zero residual disease after cytoreduction. International Federation of Gynecology and Obstetrics stage, tumor histologic type, malignant cells in fluid, grade of tumor, age, and performance status at presentation were not predictive of outcome. CONCLUSION: Colony-stimulating factor-1 in ascites may be an independent indicator of prognosis in patients with epithelial ovarian cancer.
Adult↗
Immunohistochemical localization of renin and angiotensin in the ovary: comparison between normal women and patients with histologically proven polycystic ovarian disease.
OBJECTIVE: This study was designed to test the hypothesis that the ovarian renin-angiotensin system may play a role in polycystic ovarian disease (PCOD). DESIGN: The immunohistochemical distribution of renin and angiotensin in ovaries from seven women with histologic diagnosis of PCOD was compared with that of normal ovaries. RESULTS: The large cystic follicles of polycystic ovaries (PCO) presented intense immunostaining for renin and angiotensin in both theca and granulosa cells (GCs). In developing follicles of normal ovaries, the immunostaining was restricted to the theca cell layer, with the exception of the immediately preovulatory follicles which displayed intense positivity of granulosa as well as theca cells. Atretic follicles of normal ovaries showed staining of both theca and GCs. In both normal and PCO, patches of hilus cells were intensely stained. Luteal cells also consistently stained both in normal ovaries and in the occasional corpus luteum present in polycystic ovaries. CONCLUSIONS: This study highlights the link between the ovarian renin-angiotensin system and those ovarian compartments known to be actively engaged in androgen secretion and/or luteinization and suggests that there may be an association between the ovarian renin-angiotensin system and PCOD.
Adult↗
Epithelioid angiosarcoma arising in uterine leiomyomas.
Primary angiosarcomas of the uterus are exceedingly rare. The authors report a unique case of this entity arising in connection with uterine leiomyomas. The malignant tumor cells showed focally epithelioid features and were immunoreactive for keratin. Electron microscopy and immunohistochemistry confirmed their endothelial nature.
Female↗
High-grade endometrial carcinoma in tamoxifen-treated breast cancer patients.
PURPOSE: Several reports have associated tamoxifen administration with endometrial carcinoma. A retrospective study of the histologic features of uterine cancer in patients with a history of breast carcinoma was undertaken to determine the effect of treatment with tamoxifen. MATERIALS AND METHODS: A computer search of the Yale-New Haven Hospital Tumor Registry from 1980 to 1990 identified 53 patients with a history of breast carcinoma who subsequently developed a malignant tumor of the uterine corpus. RESULTS: Fifteen patients received tamoxifen for breast carcinoma and 38 did not. The mean ages of the two groups were not significantly different. The mean interval between detection of breast and endometrial cancers was 5 years in the tamoxifen group and 12 years in the nontreated group (P = .0023). Sixty-seven percent of patients in the tamoxifen group had poorly differentiated endometrioid carcinomas (including adenosquamous carcinoma) or carcinomas associated with poor outcome (eg, uterine papillary serous carcinoma, clear-cell carcinoma, or mixed müllerian tumor), as compared with 24% in the nontreated group (P = .03). Patients in the tamoxifen group were much more likely to die of endometrial cancer (33.3% v 2.6% of the nontreated group, P = .005). CONCLUSION: From this retrospective study, it appears that women receiving tamoxifen as treatment for breast cancer who subsequently develop uterine cancer are at risk for high-grade endometrial cancers that have a poor prognosis. These findings also indicate that tamoxifen-associated uterine cancers may have a different basis from those associated with steroidal estrogen treatment.
Adenocarcinoma↗
Detection of trisomy 12 on ovarian sex cord stromal tumors by fluorescence in situ hybridization.
Trisomy of chromosome 12 has been frequently described in various neoplasms, particularly in tumors of the female genitourinary tract. Fluorescence in situ hybridization with a centromeric repetitive DNA probe, specific for chromosome 12, was done to detect such cytogenic changes on frozen-tissue sections from 10 cases of ovarian sex cord stromal tumors. The case series was composed by granulosa cell tumors (four cases), fibromas (four cases), thecoma (one case), and Sertoli-Leydig cell tumor (one case). In granulosa cell tumors, the range of trisomy was 12 to 32% and in fibromas 8 to 22%, whereas in the single case of thecoma trisomy was present in 8% and in the Sertoli-Leydig cell tumor in 4% of the nuclei examined. These results represent an additional series of cases of trisomy 12 in ovarian neoplasms, namely, in ovarian sex cord stromal tumors.
Adult↗
Primary ovarian pregnancy. A case report.
Primary ovarian pregnancy is a rare entity that is increasing in incidence. It is difficult to diagnose clinically and even intraoperatively. Conservative surgical management is advocated in young patients with good prognosis for future fertility.
Adult↗
Uterine papillary serous carcinoma after radiation therapy for carcinoma of the cervix.
This article describes the clinicopathologic features of six cases of uterine papillary serous carcinoma (UPSC), which developed several years after radiation therapy (RT) for cervical carcinoma. The possible etiologic role of radiation is discussed, and the literature on endometrial carcinomas developing after RT is reviewed.
Adult↗
Uterine papillary serous carcinoma: a study on 108 cases with emphasis on the prognostic significance of associated endometrioid carcinoma, absence of invasion, and concomitant ovarian carcinoma.
One hundred eight cases of uterine papillary serous carcinoma (UPSC) were analyzed to characterize its histologic features and biologic behavior. Special situations that could conceivably modify the behavior and therapeutic approaches were considered: (1) the occurrence of areas of endometrioid carcinoma in otherwise typical UPSC; (2) the confinement of UPSC to an otherwise benign endometrial polyp or the endometrial mucosa or absence of residual tumor at the time of hysterectomy; and (3) the coexistence of a superficial UPSC and a serous ovarian carcinoma. There was coexistence of endometrioid and UPSC in 22 cases, and tumor was confined to an endometrial polyp or endometrium in 19 cases. There was simultaneous pathologic stage I UPSC and papillary serous ovarian carcinoma in 10 cases. In patients with pathologic stages I and II UPSC the presence of areas of endometrioid carcinoma intermixed with the UPSC did not improve survival. Patients with stage I disease and no residual tumor or tumor confined to an endometrial polyp/endometrial mucosa and without vascular invasion had a survival not statistically different from those with stage I disease but with myometrial and/or vascular invasion. Patients with stage I UPSC with concomitant ovarian serous surface papillary carcinoma had survival not statistically different from patients with stage IV UPSC.
Adenocarcinoma↗
Intraabdominal hemorrhage with pulmonary large cell carcinoma metastatic to the ovary.
Secondary tumors comprise nearly 10% of ovarian malignancies; however, metastatic cancers arising from the lung are uncommon, with fewer than 15 cases reported. A patient with pulmonary large cell carcinoma and ovarian metastases resulting in recurrent refractory intraabdominal hemorrhage is presented. Metastatic involvement of the ovary from pulmonary malignancy is reviewed.
Carcinoma, Non-Small-Cell Lung↗
Intermediate filamentous proteins in adult granulosa cell tumors. An immunohistochemical study of 25 cases.
Adult granulosa cell tumors (AGCTs) are classified as sex cord-stromal tumors of the ovary. However, they may be confused with other primary ovarian neoplasms. Intermediate filaments, specifically vimentin and cytokeratins, have been identified in AGCTs by immunohistochemistry performed on frozen and formalin-fixed, paraffin-embedded tissue and two-dimensional electrophoresis. Recently, however, immunohistochemical demonstration of cytokeratin has been used as supporting evidence of epithelial rather than sex cord-stromal differentiation in ovarian neoplasia. To investigate further intermediate filamentous proteins in AGCTs, 25 such tumors were studied by immunohistochemistry in formalin-fixed, paraffin-embedded sections. Cytoplasmic staining was observed, frequently in a distinct punctate, paranuclear pattern, in 14 of 25, 14 of 25, and seven of 17 tumors using monoclonal antibodies AE1/AE3, CAM 5.2, and 35BH11, respectively, which share the ability to detect low molecular weight cytokeratins. Staining for cytokeratin was not seen in any of the 17 tumors studied using the antibody 34BE12. Twenty-three of 25 tumors showed strong positivity for vimentin, characteristically seen as globoid paranuclear staining. Nine of 25 tumors contained desmin, which was restricted to the intermixed spindle cell, cortical type stromal component of the tumors. These patterns of immunoreactivity for intermediate filaments, particularly cytokeratins, are different than in common epithelial tumors of the ovary and may be useful in the differential diagnosis of ovarian neoplasia. Moreover, the immunohistochemical detection of cytokeratins should not be used as a criterion for excluding AGCT from the differential diagnosis of an ovarian neoplasm.
Electrophoresis, Gel, Two-Dimensional↗