Pap smears in women with endometrial carcinoma.

OBJECTIVE: To correlate Pap smear findings with the histology of endometrial carcinoma and stage of the disease. STUDY DESIGN: Between 1995 and 1998, 76 women with endometrial carcinoma, having had Pap smears done within two to three months of hysterectomy at Memorial Sloan-Kettering Cancer Center, formed the basis for this study. All Pap smears and histologic sections were reviewed. RESULTS: Thirty-four patients had normal Pap smears (45%), and 42 had abnormal ones (55%). The mean age of the two groups was 65.1 and 65.2 years, respectively. Histologic subtypes included 44 International Federation of Gynecology and Obstetrics (FIGO) grade 1 endometrioid adenocarcinoma (low grade) and 32 high grade carcinomas, including 19 FIGO grade 2 or 3 endometrioid adenocarcinomas, 5 papillary serous carcinomas (PSC), 2 clear cell carcinomas (CC), 1 adenosquamous carcinoma, 3 endometrioid adenocarcinomas mixed with PSC and 2 endometrioid adenocarcinomas mixed with CC. The proportions of patients with low and high grade tumors with abnormal Pap smears were 43% (19/44) and 72% (23/32), respectively (P=.01). The proportions of patients with abnormal Pap smears and no myometrial invasion, invasion of <50% and >50% myometrial thickness were 40% (8/20), 62% (26/42) and 57% (8/14), respectively (P =.27). Vascular invasion was identified in 56% (9/16) of patients with abnormal Pap smears and in 55% (33/60) of patients with normal ones (P = .93). The proportions of patients having abnormal Pap smears with stage I and stages II, III or IV disease were 48% (30/62) and 86% (12/14), respectively (P =.01). CONCLUSION: Although the Pap smear is not a sensitive screening test for endometrial cancer and a negative Pap smear does not rule it out, this study revealed that abnormal Pap smears are significantly associated with high grade of tumor and stage II-IV endometrial carcinoma. However, they are not associated with patient age, depth of myometrial invasion or vascular invasion.

Smears diagnosed as ASCUS: interobserver variation and follow-up.

The purpose of this study was to apply atypical squamous cells of undetermined significance (ASCUS) criteria from the Bethesda System for Reporting Cervical/Vaginal Cytologic Diagnoses (TBS) to the rescreen of cases previously diagnosed as ASCUS, to compare initial and rescreen diagnoses, and to analyze agreement with follow-up (cytology or histology). Two cytotechnologists (S.B. and M.J.M.) and one cytopathology fellow (M.A.) rescreened 632 cervicovaginal specimens diagnosed as ASCUS between June 1, 1992-December 31, 1995. Age and LMP were provided. Rescreen diagnoses were categorized as within normal limits (WNL), ASCUS, low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL), or carcinoma (CA). Complete agreement was found in 200 specimens (32%): 31 (15%) WNL; 91 (45%) ASCUS; 77 (38.5%) SIL; and one (0.50%) CA. Follow-up revealed no abnormality in 67% of the cases reclassified as WNL, 49% of the cases reclassified as ASCUS, and 48% of the cases reclassified as squamous intraepithelial lesions (SIL). SIL was found in 29% of cases reclassified as WNL, 29% of specimens rediagnosed as ASCUS, and 34% of cases reclassified as SIL. Partial agreement was found in 391 specimens (62%). In 41 specimens (6%), rescreeners were in complete disagreement, and follow-up revealed 9/41 (22%) SIL or worse; 21/41 (51%) WNL; and 4/41 (10%) inconclusive. Applying established criteria, 14% (91/632) of cases diagnosed as ASCUS resulted in complete agreement, and 30% (190/632) resulted in partial agreement. Follow-up of cases initially diagnosed as ASCUS revealed SIL or CA in 30% of cases. ASCUS is a significant diagnosis warranting careful patient follow-up.

Diagnosis, pathology, staging, treatment, and outcome of epithelial ovarian neoplasia in patients age < 21 years.

BACKGROUND: Epithelial ovarian neoplasms are rare in patients under the age of 21 years. This is a report of a series of such patients documenting their presentation, histologic type, stage of disease, treatment, and outcome. METHODS: Clinical findings, histology, stage, treatment, and outcomes of 19 patients with epithelial ovarian neoplasia are reported. All histology was rereviewed. RESULTS: The median age at the time of diagnosis was 19.7 years (range, 14.1-21.8 years), and the median follow-up was 5.6 years (range, 0.2-19.5 years). The most common presenting symptom was dysmenorrhea (100%) followed by abdominal pain (68%), and the initial diagnosis usually was made ultrasonographically. There were nine (47%) serous tumors, 7 (37%) mucinous tumors, 2 (11%) small cell carcinomas, and 1 (5%) endometrioid carcinoma. Seventy-nine percent of tumors were unilateral, and 84% were low malignant potential or well differentiated tumors. Surgical treatment included unilateral salpingo-oophorectomy in 12 patients (63%), total abdominal hysterectomy and bilateral salpingo-oophorectomy in 6 patients (32%), and ovarian cystectomy in 1 patient (5%). Fifteen patients (79%) had Stage I disease, and 4 patients (21%) had Stage III disease at the time of diagnosis. There were two deaths in this series, and both occurred in patients with small cell anaplastic carcinoma. CONCLUSIONS: Epithelial ovarian neoplasias are rare in patients in this age group but must be included in the differential diagnosis of an ovarian mass. Most patients present with Stage I tumors of low malignant potential. In these patients, good survival is achieved with unilateral salpingo-oophorectomy and preservation of fertility. In contrast, small cell carcinomas are very aggressive, and patients with this variant require intensive therapy.

Paclitaxel-based chemotherapy in carcinoma of the fallopian tube.

OBJECTIVE: The objective of this study was to determine the clinical outcomes of patients with fallopian tube carcinoma treated with paclitaxel-based combination chemotherapy following primary cytoreductive surgery. METHODS: Twenty-four patients with the diagnosis of primary tubal adenocarcinoma treated between 1993 and 1998 were identified through the gynecology service database and the Memorial Sloan-Kettering Cancer Center tumor registry. Medical records were reviewed for information on age, stage, chemotherapy regimen, surgical intervention, relapse, and survival. All patients had their histologic material initially read or reviewed at Memorial Sloan-Kettering Cancer Center prior to treatment. The original slides were reviewed again by one of the authors (P.E.S.) to confirm the diagnosis of primary fallopian tube cancer. RESULTS: The mean age of the patients was 63 years (range, 44-76). Distribution by stage was as follows: four patients (17%) were Stage I, three patients (12%) were Stage II, 16 patients (67%) were Stage III, one patient (4%) was Stage IV. Four patients had grade 2 tumors, 20 had grade 3. Sixteen patients (67%) had optimal cytoreduction at the time of initial surgery with residual disease less than 1 cm. Eight patients (33%) had suboptimal cytoreduction. Following initial surgery, all patients were treated with paclitaxel-based chemotherapy for a median of five cycles. Twenty-three patients received paclitaxel at the dose of 135-175 mg/m(2) in combination with carboplatin or cisplatin; the majority, 17 of 23 (74%), received carboplatin. One patient received paclitaxel alone. Median follow-up from time of initial surgery was 24 months (range, 1-73 months). Two patients are dead of disease. Overall survival for the entire group was 96% at 12 months by Kaplan-Meier analysis, and 90% at 3 years. The overall median progression-free survival was 27 months (range, 5-57 months) for the entire group. The median disease progression-free survival at 3 years was 67% (95% CI, 45-100) in the optimally debulked group as compared with 45% in the suboptimally debulked group (95% CI, 27-57). Twelve patients (50%) had evidence of recurrence or persistent disease. There were fewer recurrences in the optimally debulked group: 5 of the 16 patients (31%) versus 7 of the 8 patients (88%) with suboptimal cytoreduction. CONCLUSION: Optimally cytoreduced patients with primary fallopian tube carcinoma treated with a paclitaxel-based chemotherapy regimen have an excellent possibility of survival.

Effect of adjuvant tamoxifen on the endometrium in women with breast cancer: a prospective study using office endometrial biopsy.

PURPOSE: To determine the frequency of developing abnormal pathologic changes in the endometria of tamoxifen-treated women. To characterize the type of pathologic changes involved. PATIENTS AND METHODS: Between October 1991 and September 1998, 159 patients initiating tamoxifen therapy for breast cancer confined to the breast and axillary lymph nodes were entered in a prospective study. In this study, office endometrial biopsies (EMBs) were obtained during the initiation of tamoxifen and at 6-month intervals for a 2-year period. Three subsequent annual EMBs were recorded for each patient, amounting to a 5-year surveillance. RESULTS: One hundred fifty-nine patients with a median age of 50 years were entered onto study. Patients were assessable if EMBs were performed at least 1 year after the initiation of tamoxifen treatment. Nine patients (5. 7%) were considered protocol violations. The remaining 111 assessable patients underwent a total of 635 EMBs (mean, 5.8 EMBs), with a median surveillance time of 36 months. Eighty-two (12.9%) of the 635 biopsies revealed tissue insufficient for diagnosis. Fourteen patients (12.6%) underwent dilation and curettage (D&C) for an abnormal EMB, persistent bleeding, or for evaluation of adnexal masses at the time of laparoscopy. Findings at D&C included complex hyperplasia (n = 1), abnormal histiocytes (n = 1), simple hyperplasia (n = 2), polyps (n = 4), endocervical polyp (n = 1), and decidualization (n = 2). Three D&Cs were negative. Three patients have undergone hysterectomy. CONCLUSION: EMB was used to monitor the endometrium in the majority (95%) of breast cancer patients on tamoxifen in this trial, but the utility of routine EMB for screening in tamoxifen-treated women seems limited.

Peritoneal washings in endometrial carcinoma. A study of 298 patients with histopathologic correlation.

OBJECTIVE: To correlate findings of peritoneal washings in patients with endometrial carcinoma with histologic parameters. STUDY DESIGN: Between 1995 and 1998, 298 women with endometrial carcinoma were treated by hysterectomy with intraoperative peritoneal washings (PW) at Memorial Sloan-Kettering Cancer Center. All cytology and pathology slides were available for review. Pathologic parameters of hysterectomy specimens were evaluated and correlated with the findings of PW. RESULTS: Thirty-two patients (10.7%) had abnormal PW. Two hundred sixty-two had endometrioid adenocarcinoma; 26 of them had abnormal PW (10.0%). Thirty-six patients had other histologic subtypes (papillary serous carcinoma, clear cell carcinoma and adenosquamous carcinoma), and six of them had abnormal PW (16.7%). The incidence of abnormal PW in the two groups was not significantly different (P = .78). Among 26 patients with endometrioid adenocarcinoma and abnormal PW, there were 17 cases (9.9%) of International Federation of Gynecology and Obstetrics (FIGO) grade 1, 7 (12.7%) of grade 2 and 2 (5.7%) of grade 3 (P = .56). Ten cases (14.9%) had no myometrial invasion, 10 (7.0%) had myometrial invasion of < or = 50% of myometrial thickness, and 6 (11.5%) had invasion of > 50% of myometrial thickness (P = .18). Vascular invasion was present in 8 cases (14.8%) and absent from 17 (8.2%) (P = .14). Eighteen patients (7.6%) had stage I/II disease, and eight patients (30.8%) had stage III/IV disease (P = .001). Among 298 patients, cervicovaginal smears performed before surgery were available for review in 76. Five of the 7 patients (71.4%) with abnormal PW and 37 of the 69 patients (53.6%) with normal PW had abnormal Pap smears (P = .45). CONCLUSION: Abnormal PW did not correlate with histologic subtypes, FIGO grade, depth of myometrial invasion, vascular invasion or abnormal Pap smears. A significantly higher incidence of abnormal PW was associated with stage III/IV disease.

Absence of premalignant histologic, molecular, or cell biologic alterations in prophylactic oophorectomy specimens from BRCA1 heterozygotes.

BACKGROUND: The high mortality associated with ovarian carcinoma is largely a reflection of the inability to diagnose the disease at an early stage; the identification of a histologic lesion or molecular marker associated early stages of transformation would represent an important advance in understanding the natural history of this cancer. The existence of individuals with germline mutations in the ovarian and breast carcinoma susceptibility gene BRCA1 represents a unique opportunity to search for such premalignant alterations in ovarian tissues that are at unusually high risk for tumorigenesis. In this study, the authors addressed the hypothesis that pathologically normal ovaries removed from BRCA1 heterozygotes are likely to display premalignant histologic, molecular, and/or cell biologic alterations that may provide insight into early stages of ovarian tumorigenesis. METHODS: Ovarian tissues from 18 BRCA1 heterozygotes and from 20 age-matched controls were examined in a blinded fashion for histologic evidence of surface epithelial pseudostratification, epithelial inclusion cysts, deep cortical invaginations of surface epithelium, increased stromal cell activity, and surface papillomatosis. Immunohistochemical analyses for expression of BRCA1, p53, and ERBB-2 and quantitation of cell proliferation (Ki-67 expression) and apoptosis (TUNEL assay), were also performed on all specimens. RESULTS: Although histologic alterations were observed, there was no difference in frequency between cases and controls. Analysis of BRCA1 expression revealed ubiquitous nuclear immunoreactivity in the surface epithelial cells of all ovaries. Similarly, no evidence was found of p53 overexpression in any ovarian tissue or of a difference in ERBB-2 expression between cases and controls. Finally, no differences were observed in epithelial cell proliferation or apoptosis. CONCLUSIONS: Clinically, normal ovaries from BRCA1 heterozygotes do not show evidence of premalignant alterations in histology, molecular markers, cell proliferation, or apoptosis, indicating that such changes are likely rare.

Association between initial diagnostic procedure and hysteroscopy and abnormal peritoneal washings in patients with endometrial carcinoma.

BACKGROUND: Hysteroscopy has been implicated in the finding of positive peritoneal washings (PW) in patients with endometrial carcinoma in several case reports. The current study was designed to evaluate whether there was an increased incidence rate of positive peritoneal washings in patients after hysteroscopy compared with patients who did not undergo hysteroscopy. METHODS: Two hundred eighty-four women with endometrial carcinoma were treated by hysterectomy with intraoperative PW at the Memorial Sloan-Kettering Cancer Center between 1995-1998. They were diagnosed by either endometrial biopsy (EMB) or dilatation and curretage (D & C) with or without hysteroscopy during the same period. RESULTS: Of 173 patients diagnosed by EMB, 16 had abnormal PW (9.2%). Of 111 patients diagnosed by D & C, 11 had abnormal PW (9.9%). There was no significant difference between the two groups (P = 0.85). Of 23 patients who were diagnosed by D & C with hysteroscopy, 3 had abnormal PW (13.0%). Of 177 patients who did not undergo hysteroscopy, 17 had abnormal PW (9.6%). Of 84 patients for whom information regarding hysteroscopy was not available, 7 had abnormal PW (8.3%). The incidence rates among the three groups were not significantly different (P = 0.79). CONCLUSIONS: The initial diagnostic procedure, including hysteroscopy, does not appear to be associated with a high incidence rate of abnormal PW in patients with endometrial carcinoma.

Clinicopathologic features of BRCA-linked and sporadic ovarian cancer.

CONTEXT: Most hereditary ovarian cancers are associated with germline mutations in BRCA1 or BRCA2. Attempts to define the clinical significance of BRCA mutation status in ovarian cancer have produced conflicting results, especially regarding survival. OBJECTIVE: To determine whether hereditary ovarian cancers have distinct clinical and pathological features compared with sporadic (nonhereditary) ovarian cancers. DESIGN AND SETTING: Retrospective cohort study of a consecutive series of 933 ovarian cancers diagnosed and treated at our institution, which is a comprehensive cancer center as designated by the National Cancer Institute, over a 12-year period (December 1986 to August 1998). PATIENTS: The study was restricted to patients of Jewish origin because of the ease of BRCA1 and BRCA2 genotyping in this ethnic group. From the 189 patients who identified themselves as Jewish, 88 hereditary cases were identified with the presence of a germline founder mutation in BRCA1 or BRCA2. The remaining 101 cases from the same series not associated with a BRCA mutation and 2 additional groups (Gynecologic Oncology Group protocols 52 and 111) with ovarian cancer from clinical trials (for the survival analysis) were included for comparison. MAIN OUTCOME MEASURES: Age at diagnosis, surgical stage, histologic cell type and grade, and surgical outcome; and response to chemotherapy and survival for advanced-stage (II and IV) cases. RESULTS: Hereditary cancers were rarely diagnosed before age 40 years and were common after age 60 years, with mean age at diagnosis being significantly younger for BRCA1- vs BRCA2-linked patients (54 vs 62 years; P=.04). Histology, grade, stage, and success of cytoreductive surgery were similar for hereditary and sporadic cases. The hereditary group had a longer disease-free interval following primary chemotherapy in comparison with the nonhereditary group, with a median time to recurrence of 14 months and 7 months, respectively (P<.001). Those with hereditary cancers had improved survival compared with the nonhereditary group (P=.004). For stage III cancers, BRCA mutation status was an independent prognostic variable (P=.03). CONCLUSIONS: Although BRCA-associated hereditary ovarian cancers in this population have surgical and pathological characteristics similar to those of sporadic cancers, advanced-stage hereditary cancer patients survive longer than nonhereditary cancer patients. Age penetrance is greater for BRCA1-linked than for BRCA2-linked cancers in this population.

Effects of tamoxifen on cervicovaginal smears from patients with breast cancer.

OBJECTIVE: To evaluate the effect of tamoxifen on cervicovaginal epithelium and determine the value of cervicovaginal smears in identifying patients at risk for endometrial carcinoma. STUDY DESIGN: A group of 48 women with prior breast cancer were divided into three groups: A, tamoxifen-treated patients who developed endometrial carcinoma (n = 20); B, patients with endometrial cancer not treated with tamoxifen (n = 22); and C, tamoxifen-treated patients with no endometrial carcinoma (n = 16). A total of 114 cervicovaginal smears from these patients were evaluated for maturation index, histiocytes, benign and malignant endometrial cells, reactive cellular changes and microorganisms. All patients treated with tamoxifen had received doses of 10 mg twice daily. RESULTS: The maturation index was increased in tamoxifen-treated patients (A and C) versus nontreated patients (B) P < or = .001). The number of cases with endometrial cells was significantly higher in smears of treated patients who developed endometrial cancer (A) as compared to groups B and C (P = .01 and .02, respectively). Histiocytes were also significantly increased in the two groups that subsequently developed endometrial carcinoma (A and B) as compared to the group that did not (group C) (P = .02). There was no significant difference in the presence of reactive cellular changes between the three groups. CONCLUSION: Patients treated with tamoxifen exhibited a partial estrogenic effect in their smears regardless of whether they developed endometrial cancer. However, the presence of endometrial cells in the smears indicated a higher risk of endometrial adenocarcinoma.

Carcinosarcoma of the ovary in a patient with a germline BRCA2 mutation: evidence for monoclonal origin.

BACKGROUND: Themajority of hereditary breast and ovarian cancers are associated with germline mutations in BRCA1 or BRCA2. While the occurrence of breast carcinoma and epithelial ovarian carcinoma in association with BRCA mutations is firmly established, the etiologic role of these genes in the development of other tumor types is less well documented. Carcinosarcoma of the ovary is an uncommon tumor consisting of both malignant epithelial and malignant mesenchymal components. OBJECTIVE: Here we report a patient with an ovarian carcinosarcoma who was found to harbor a germline mutation in BRCA2. We sought to link the BRCA2 mutation to the pathogenesis of this tumor as well as to determine whether both histologic components arose from the same progenitor cell. METHODS: Microdissection and molecular genetic analyses of the carcinomatous and sarcomatous components of this tumor were performed. RESULTS: Clonal loss of the wild-type BRCA2 allele as well as the same somatic mutation of the TP53 gene was evident in both histologic components. CONCLUSIONS: These data indicate that hereditary ovarian carcinosarcoma may result from a mutation in BRCA2 and that both histologic elements of this tumor arose from the same progenitor cell.

Selection of carbohydrate antigens in human epithelial ovarian cancers as targets for immunotherapy: serous and mucinous tumors exhibit distinctive patterns of expression.

Expression of blood group-related carbohydrate antigens was examined in frozen sections from a series of ovarian carcinomas of different histological types using an indirect immunoperoxidase technique. Antigenic specificities belonging to the O(H) and Lewis blood group families (H-1, H-2, Le(a), sLe(a), Le(x), sLe(x), Le(b) and Le(y)) or the mucin-core family (Tn, sTn and TF) were studied. A distinct difference in antigen expression between mucinous and other ovarian carcinomas (serous and endometrioid) was observed. Specifically, mucinous tumors tended to express sTn, Le(a) and sLe(a) strongly and homogeneously, whereas serous and endometrioid tumors rarely expressed these specificities and, in contrast, expressed Le(y) and H type 2 antigen strongly. When expressed in serous tumors, sTn was usually distributed in a heterogeneous pattern, whereas sTn expression in mucinous tumors was much more homogeneous. The distribution of Le(y) in serous tumors was noticeably homogeneous. H-1, Le(x), sLe(x), Le(b), TF and Tn specificities were rarely expressed in any type of ovarian carcinoma. Our results provide further support for the different histogenesis of mucinous and non-mucinous tumors and indicate alternative differentiation pathways for the 3 pathological subtypes of ovarian tumor. They also provide the basis for the choice of carbohydrate antigens for active and passive immunotherapy of ovarian carcinomas.

The accuracy of frozen-section diagnosis in metastatic breast and colorectal carcinoma to the adnexa.

OBJECTIVE: The objective of our study was to describe the accuracy of intraoperative frozen-section diagnosis of carcinoma metastatic to the adnexa in women with a history of breast or colorectal carcinoma. METHODS: We conducted a retrospective chart review of all patients with a history of breast or colorectal carcinoma who developed histologically proven pelvic or abdominal metastases between 1988 and 1995. In those patients whose final histologic review revealed carcinoma metastatic to the adnexa, the accuracy of the intraoperative frozen-section diagnosis of the adnexal tumor was compared to the final diagnosis. RESULTS: Forty-three patients were identified and in 36 patients the frozen section was obtained from the adnexa. Twenty-one patients (58.3%) had metastatic breast carcinoma and 15 (41.7%) had metastatic colorectal carcinoma to the adnexa. Carcinoma in the adnexa was correctly diagnosed by frozen section in 35 of 36 patients (97.2%). Metastatic carcinoma was identified at frozen section in 17 of 21 patients (81%) with metastatic breast cancer and 13 of 15 patients (86.7%) with metastatic colorectal cancer. In 3 of 21 patients (14.3%) with metastatic breast cancer and in 2 of 15 patients (13.3%) with metastatic colorectal cancer, the frozen-section diagnosis was carcinoma of uncertain origin. One patient had a false-negative frozen section because the small focus of metastatic breast cancer was not sampled at the time of frozen section. CONCLUSION: Intraoperative frozen-section evaluation correctly diagnosed carcinoma in the adnexa in 97% of patients, and in over 80% of cases, the carcinoma was diagnosed as being metastatic in origin.

Molecular genetic characterization of BRCA1- and BRCA2-linked hereditary ovarian cancers.

Hereditary ovarian cancers associated with germline mutations in either BRCA1 or BRCA2 were studied to determine whether somatic mutation of the P53 gene is required for BRCA-linked ovarian tumorigenesis and further, whether the spectrum of additional somatic molecular genetic alterations present in these tumors differs from that known to exist in sporadic ovarian cancers. Forty tumors, 29 linked to BRCA1 and 11 linked to BRCA2, were examined for mutational alterations in P53, K-RAS, ERBB-2, C-MYC, and AKT2. The presence of a P53 mutation in 80% of these cancers indicates that P53 mutation is common but not required for BRCA-linked ovarian tumorigenesis; notably, a significantly higher proportion of the P53 mutations in BRCA2-linked cancers were deletions or insertions compared with the more typical spectrum of missense mutations seen in BRCA1-linked cancers. Additionally, BRCA-linked ovarian carcinomas seem to develop through a unique pathway of tumorigenesis that does not involve mutation of K-RAS or amplification of ERBB-2, C-MYC, or AKT2.

A case-case analysis of factors related to overexpression of p53 in endometrial cancer following breast cancer.

We studied 54 patients diagnosed with endometrial cancer between 1981 and 1994 following a diagnosis of breast cancer. We used a case-case analysis, comparing tumors with and without overexpression of the p53 gene product to evaluate the association of putative p53 mutations with tamoxifen use and other risk factors for endometrial cancer. Twenty-four % of the tumors showed strong positive staining for the p53 gene product. Tumors in a more advanced stage (stage 2, 3, or 4, compared to stage 1) were more likely to overexpress p53 [odds ratio (OR) = 4.2; 95% confidence interval (CI), 1.1-16.2], as were tumors with serous or clear cell, compared to endometrioid, histology (OR = 5.8; 95% CI, 1.3-26.5). There was a small association between p53 overexpression and treatment with tamoxifen for breast cancer (OR = 2.6; 95% CI, 0.69-9.8). There was a strong relationship between overexpression of p53 and having a first-degree relative with breast cancer (OR = 12.3; 95% CI, 2.6-57.4) and between overexpression of p53 and having an additional cancer, i.e., at sites other than breast or endometrium (OR = 7.9; 95% CI, 1.6-40.1). In this group of women, genetic predisposition to cancer, as reflected in family history of breast cancer and personal history of an additional primary cancer, was strongly associated with overexpression of p53 in endometrial tumors. The results suggest that use of tamoxifen may be associated with an increase in tumors that overexpress p53, although the results could be due to chance.

The role of whole-pelvic irradiation in the treatment of early-stage uterine carcinosarcoma.

Thirty-eight patients with Stage I and II uterine carcinosarcoma were treated by surgery with and without whole-pelvic irradiation (WPI) at our institution from 1975 to 1993. Ten patients (8 Stage I and 2 Stage II) were treated with surgery alone, while 28 patients (20 Stage I and 8 Stage II) received WPI in addition to surgery. With a median follow-up of 75 months (range 25-220 months), a trend toward a decreased rate of pelvic recurrence in those receiving WPI (6/28, 21%) compared to those treated with surgery alone (5/10, 50%) was observed (P = 0.09). There was no difference in the rate of distant recurrence between those receiving WPI (12/28, 43%) and those who did not (4/10, 40%) (P = 0.9). There was also no difference in the 2- and 5-year Kaplan-Meier survival estimates for the patients receiving WPI (79 and 59%, respectively) compared to those who did not receive WPI (60 and 60%, respectively) (P = 0.84). In this small series, the addition of whole-pelvic irradiation to primary surgery did not improve survival; however, a trend toward improved pelvic control was observed, suggesting a possible benefit for pelvic irradiation that should be studied in future trials.

Platinum-based chemotherapy for advanced-stage serous ovarian carcinoma of low malignant potential.

PURPOSE: To evaluate the effect of platinum-based chemotherapy on tumor response in patients with advanced-stage serous ovarian carcinoma of low malignant potential. PATIENTS AND METHODS: We conducted a retrospective review of hospital records, pathology slides, and office charts of patients identified as having Stage III or IV serous ovarian cancer of low malignant potential. RESULTS: Between November 1979 and April 1993, 21 patients with advanced-stage serous ovarian carcinoma of low malignant potential received platinum-based chemotherapy following initial cytoreductive surgery. The amount of residual disease was recorded in 20 patients; 8 (40%) had macroscopic residual tumor < 2 cm in largest diameter, and 12 (60%) had only microscopic disease. Sixteen patients underwent a second-look laparotomy following chemotherapy; 10 (62.5%) had no evidence of disease, 1 (6%) had a partial response, 2 (12.5%) had stable disease, and 3 (19%) had progressive disease. During a mean follow-up of 64 months, only 1 patient had died of disease. She had progressive disease noted at second-look laparotomy. Five of 6 patients who did not have a complete response to initial chemotherapy underwent further therapy with oral etoposide (1), intraperitoneal platinum (2), intraperitoneal mitoxantrone (1), or both (1). The sixth patient received no further therapy. Three of the patients subsequently receiving salvage intraperitoneal therapy underwent a third-look laparotomy. Two had partial responses noted, while the third patient had stable disease. CONCLUSIONS: Platinum-based chemotherapy is effective in achieving surgically documented responses in patients with advanced-stage serous ovarian tumors of low malignant potential. The benefit of this therapy in improving survival is unproven.

Genital ulcer disease in women infected with human immunodeficiency virus.

OBJECTIVE: The purpose of this study was to determine the prevalence and microbiologic characteristics of genital ulcer disease in a population of human immunodeficiency virus-infected women. STUDY DESIGN: A retrospective cohort study was performed in university-affiliated, hospital-based women's human immunodeficiency virus clinics. A total of 307 women with human immunodeficiency virus infection were followed up during 20 months. There were no interventions. Age, race, CD4+ cell counts, bacteriologic and virologic analyses in cases of ulcers, serologic testing for syphilis, and histopathologic examination in selected cases (n = 6). RESULTS: Among 307 women followed up over a 20-month period, 43 ulcers were detected with a prevalence of 14%. Among the ulcer cases the average absolute CD4+ lymphocyte number was 210/mm3. Diagnostic evaluation yielded no proven etiologic agent in 26 (60%) of the cases. Twelve of the 43 cases (28%) were positive for herpes simplex-2. Five cases (12%) yielded unusual or mixed bacteriologic types. No cases were attributable to primary syphilis infection. One case each of an ulcer infected with cytomegalovirus, Chlamydia trachomatis, and Gardnerella vaginalis, as well as three unusual presentations of herpetic ulcers, is analyzed in detail. CONCLUSION: These cases exemplify the often dramatic presentation of human immunodeficiency virus-related genital ulcers and the clinical complexity of both diagnosis and management. The frequent lack of an infectious or neoplastic cause in human immunodeficiency virus-infected women with genital ulcer disease suggests that human immunodeficiency virus may play a local role in causation or exacerbation. Biopsies of atypical genital ulcers should be considered to aid diagnosis. Further studies are needed to elucidate the pathogenesis of genital ulcer disease in human immunodeficiency virus-infected women.

Enhanced detection of bladder cancer in urine cytology with Lewis X, M344 and 19A211 antigens.

Lewis X, M344 and 19A211, all glycoprotein antigens associated with bladder tumors, were evaluated in urine cytologic specimens from 52 patients with transitional cell bladder neoplasms and from 12 controls. Forty-three of 52 patients had a tumor on a concurrent bladder biopsy, while 9 of 52 patients had a negative biopsy. Of the 43, 27 (62.8%) had positive or suspicious cytology, 35 (81.4%) had positive immunocytochemical reactions with at least one antibody, and 36 (83.7%) had either cytologic or immunocytochemical abnormalities. Of the 15 patients with a low grade tumor (papilloma or grade 1 transitional cell carcinoma), 14 (93.3%) had positive immunohistochemical findings, while 6 (40%) had recognizable abnormal cells on routine cytology. Of 28 patients with a high grade tumor, 21 (75%) had positive immunohistochemical findings, while 21 (75%) had abnormal cytology. Staining of rare epithelial cells was seen in 2 of 12 control cases (specificity, 83.3%). Immunocytochemistry with antibodies to tumor-associated antigens can enhance the cytologic detection of exfoliated low grade bladder epithelial tumor cells.