Paraneoplastic cerebellar degeneration in ovarian carcinoma: case report with review of immune modulation.

Paraneoplastic cerebellar degeneration (PCD) is a rare nonmetastatic complication of a carcinoma. It is typically mediated by antibodies generated against tumor antigens. These antigens are the same proteins as expressed on Purkinje cells within the cerebellum; immune activation in the central nervous system (CNS) results in the syndrome. A 56-year-old woman with stage IIIC serous ovarian carcinoma diagnosed 3 years prior developed progressive limb ataxia. Serum anti-Yo antibodies were positive, confirming the diagnosis of PCD. Treatment with plasmaphoresis, intravenous immune globulin, and immune modulation with corticosteroids and tacrolimus was unsuccessful. Although the syndrome can be debilitating and treatment options are limited, it may also be an example of a successful host immune response in certain cases.

The second-look operation improves survival in suboptimally debulked stage III ovarian cancer patients.

In a single-institution retrospective cohort study, 230 patients were treated for stage III primary ovarian cancer and 175 became eligible for second-look operations by virtue of a complete clinical response after primary surgical cytoreduction and platinum-based combination chemotherapy. Of these, 109 underwent a second-look operation. Optimal primary cytoreduction was defined as residual disease < or =1 cm. Median follow-up was 68.3 months. Five-year survival for all the 230 stage III ovarian cancers was 43.4%. Among all eligible patients (n = 175), there was no survival difference (P = 0.67) in those having second look (57.3%, 5-year survival) versus no second look (48.7%). In those patients with optimal primary cytoreduction (n = 118), there was no survival advantage to second look (69% versus 61%, P = 0.7). However, in those with suboptimal primary cytoreduction (n = 47), 5-year survival was 36% in those having second look versus only 13% in those refusing second look (P < 0.05). Multivariate analysis identified second-look surgery as the only significant independent prognostic variable affecting survival (RR = 0.321, P < 0.04). Patients with suboptimal debulking at primary surgery for stage III ovarian cancer appear to achieve a survival benefit from second-look surgical procedures, presumably from the early identification and treatment of residual disease.

Founder BRCA 1 and 2 mutations among a consecutive series of Ashkenazi Jewish ovarian cancer patients.

OBJECTIVE: The purpose of this study was to describe the incidence of the three Ashkenazi Jewish founder genetic BRCA 1 and 2 mutations among an unselected, consecutive group of Ashkenazi Jewish ovarian cancer patients. MATERIALS AND METHODS: From 7/30/96 to 4/12/99, 92 Ashkenazi Jewish patients with histologically confirmed epithelial ovarian cancer had surgery. All of these patients had DNA extracted from 5-microm sections of their paraffin-embedded surgical specimen tissue blocks using the Qiagen QIAamp tissue extraction kit. A multiplex (triplex) polymerase chain reaction was performed to amplify fragments for the 185delAG, 5382insC, and 6174delT mutations. The products were hybridized with normal and mutant probes for each of the three mutations. All clinical data were collected retrospectively and statistical significance was evaluated using the chi(2) test or a two-tailed Fisher's exact test, depending on the sample size. RESULTS: There were 23 patients positive for one of the three founder BRCA mutations. Fourteen patients were positive for the 185delAG mutation, 2 patients were positive for the 5382insC mutation, and 7 patients were positive for the 6174 delT mutation (61, 9, and 30%, respectively). This represented a 25% incidence (95% CI: 16-34%) of one of the three founder BRCA mutations among our 92 Ashkenazi Jewish ovarian cancer patients. None of the patients was positive for more than one mutation. There was no statistically significant difference in parity, histology, grade, or stage between the BRCA founder mutation positive and negative patients. The difference between the percentage of mutation carriers among patients with one affected first-degree relative (13/22 or 59%) compared to those without at least one affected first-degree relative (10/70 or 14%) was highly significant (P = 0.001). CONCLUSIONS: Ashkenazi Jewish ovarian cancer patients represent a group with a high likelihood of being carriers of BRCA 1 and 2 genetic mutations, regardless of family history. As a result, all ovarian cancer patients who are of Ashkenazi Jewish descent should be counseled regarding BRCA 1 and 2 genetic screening, as well as the potential implications of these results for the patient as well as her relatives in terms of prognosis, screening, chemoprevention, and consideration of prophylactic surgical procedures.

Morphometric Characterization of HPV-Related Lesions of Uterine Cervix.

OBJECTIVES: This study addresses three issues related to human papillomavirus (HPV) cervical lesions: identification of HPV in histologic normal tissue, identification of HPV subtypes with risk for cervical cancer, and histologic differences between HPV not associated to cervical intraepithelial neoplasia (CIN1) lesions (condyloma) and HPV associated to CIN1 lesions. MATERIALS AND METHODS: The authors histologically classified 48 cervical biopsy slides into three groups: normal (n = 22), condyloma (n = 20), and CIN1 (n = 6). Morphometric analyses of nuclear and cytoplasmic ratio for area, length, and diameter of 25 cells per case were performed. Histologic reports and in situ hybridization for HPV subtype were compared to morphometric data to assess correlation among them. RESULTS: Using image analysis, the authors correctly classified all cases except two into histologic or in situ hybridization diagnosis. Morphometry helped identify viral changes in cells that appeared histologically normal, HPV subtype at risk in condyloma lesions, and condyloma from those combining HPV lesions and CIN1. CONCLUSIONS: There were enough data supporting morphometric distinction of HPV-related cervical lesions assessed by nuclear and cytoplasmic ratio.

Laparoscopic lymphadenectomy for gynecologic malignancies.

OBJECTIVE: The purpose of our study was to detail our 5-year experience with laparoscopic lymphadenectomy for gynecologic malignancies. METHODS: From 11/5/92 to 3/9/98, we performed laparoscopic lymphadenectomies on 94 patients with various gynecologic malignancies. Pelvic, paraaortic, and combinations of both pelvic and paraaortic lymphadenectomies were performed depending on the primary site of disease and indication for lymph node dissection. Data were prospectively collected on all patients. RESULTS: From 11/5/92 to 3/9/98 we performed 94 laparoscopic lymphadenectomies for gynecologic malignancies. The distribution included 64 patients with cervical cancer, 14 with ovarian cancer, 12 with endometrial cancer, 2 with fallopian tube cancer, 1 with a uterine malignant mixed mesodermal tumor, and 1 with a metastatic neuroendocrine tumor. Fifty-five patients had only pelvic lymph node dissections, 9 patients had paraaortic dissections only, and 30 had both pelvic and paraaortic dissections performed. Among 30 patients having laparoscopic lymphadenectomy only, the mean hospital stay was 3.6 days. Included in this group were 19 patients who received postoperative neoadjuvant chemotherapy for cervical cancer as inpatients prior to ambulatory radiation therapy. The mean length of stay for this group was 4.6 days versus 1.7 days for the 11 patients who did not receive postoperative chemotherapy (P = 0.0025). The mean number of pelvic nodes was 11.9 (range 0-57), with a mean of 4. 5 between 11/5/92 and 12/31/95 and a mean of 19.1 from 1/1/96 to 3/9/98. The mean number of paraaortic nodes obtained was 3.7 (range 0-14), with a mean of 3.4 from 11/5/92 to 12/31/95 and a mean of 4.1 from 1/1/96 to 3/9/98. A total of 3 patients required conversions to laparotomy. One was for a vascular injury to the vena cava, 1 for a large tumor extending to both sidewalls, and the third for removal of densely matted lymph nodes. CONCLUSIONS: Laparoscopic lymphadenectomy is a technically feasible procedure for patients with gynecologic malignancies requiring lymph node dissections, with an acceptable safety profile and nodal yield. The number of nodes obtained increased in direct proportion to operator experience. In addition, patients may benefit from a decrease in hospital stay compared to conventional lymphadenectomy via laparotomy.

Interphase fluorescence in situ hybridization studies of ovarian adenocarcinomas using the midisatellite probe.

The genes involved in ovarian carcinogenesis are largely unknown. Cytogenetic studies have shown a large number of chromosomal abnormalities in ovarian cancers. Molecular studies have additionally found abnormalities. Few in situ hybridization studies have been performed on ovarian cancer tissues. We chose to study the distal region of chromosome 1p with the midisatellite probe and interphase fluorescence in situ hybridization. A total of 35 patient samples, including various controls and cancers, was collected from our pathology archives. Our cancer cases included some patients with stage I disease, in whom tumors arose in endometriotic cysts. In these cases, both tumor tissue and areas in the cyst distant from the tumor mass were examined. Results showed clear cell carcinoma nuclei to have an increase in both number and size of probe signals, interpreted as representing amplification of the probed region of chromosome 1. Serous carcinomas showed an increase in the number of signals, up to four. We felt this could be a result of amplification, or, because these cells exhibited the highest mitotic counts, to DNA doubling in preparation for mitosis. Endometrioid carcinomas resembled controls in showing up to two small probe signals, but not more. We conclude that amplification in distal chromosome 1p occurs in ovarian clear cell, and possibly serous, carcinomas and may not be important in endometrioid carcinomas. Because alteration was not found in the various control epithelia, including nonmalignant-looking areas from cysts which also contained cancer, we believe that the change, when present, may not be an early step in carcinogenesis.

Laparoscopic management of adnexal masses in premenopausal and postmenopausal women.

OBJECTIVE: To evaluate the feasibility and safety of laparoscopic adnexal mass removal in patients without preselection for benign pathology and assess the operative complications and findings. METHODS: All patients presenting to the gynecologic oncology service between April 1992 and April 1996 with adnexal masses were candidates for laparoscopic management. Patients underwent preoperative radiological studies and office pelvic examination. Laparoscopic management was attempted on patients without evidence of gross metastatic disease or masses that extended above the umbilicus. Laparotomy was performed if indicated by pathologic findings or technical difficulty. All removed adnexal masses were sent for immediate pathologic diagnosis. The type of procedure, intraoperative findings, and complications were all recorded at the time of procedure. RESULTS: One hundred sixty patients underwent laparoscopic evaluation for an adnexal mass. Benign pathology was discovered in 139 (87%, 95% confidence interval [CI] 84, 90) patients, and 141 (88%, 95% CI 86, 91) patients were managed laparoscopically. Reasons for laparotomy included technical difficulty, operative complications, or malignancy. Frozen section diagnosis was concordant with the final pathology reports in all but five patients (97% concordance), and no discrepancies resulted in treatment delays. CONCLUSION: Laparoscopic management of adnexal masses can be successful in a gynecologic oncology population if there is expertise in operative laparoscopy, availability of immediate accurate pathologic examination, and appropriate further treatment where indicated.

The impact of laparoscopic surgery in the management of adnexal masses.

The objective of this study is to evaluate the clinical aspects of laparoscopic management of adnexal masses. The feasibility of this approach has been demonstrated, but the safe and effective use of laparoscopy for this indication requires training, technical skills and experience on the part of the laparoscopist. If used appropriately, many patients will benefit from minimally-invasive surgery. We compared clinical factors of patients having laparoscopy to those having laparotomy in a case-control study of 30 patients with adnexal masses. Oophorectomy or ovarian cystectomy was performed by laparoscopy for 20 women and by laparotomy for 10 women. Comparing the 2 groups, the most significant difference was the decrease in length of hospital stay in the laparoscopy group. There were no significant differences in operative time or intraoperative complications. Estimated blood loss was lower in the laparoscopy group, and no intraoperative complications occurred. No patient required conversion from laparoscopy to laparotomy. All patients had benign disease despite the inclusion of patients with risk factors for ovarian carcinoma. This study clearly demonstrates the clinical benefits of laparoscopic management of adnexal masses treated with oophorectomy or ovarian cystectomy.

Results of selective use of operative laparoscopy in gynecologic oncology.

OBJECTIVE: To evaluate the impact of integration of operative laparoscopy on length of stay (LOS) and complication rates on an academic gynecologic oncology service. METHODS: Retrospective analysis of all admissions to our gynecologic oncology service was performed for the academic years 1990/1991 and 1993/1994. Primary endpoints were frequency of complications and LOS. RESULTS: In 1990/1991, there were 785 total admissions, of which 287 were surgical and 3% were approached laparoscopically. In 1993/1994, there were 973 admissions of which 436 were surgical and 23% were approached laparoscopically. Operative laparoscopy was applied equally regardless of age and reproductive status; the utilization of laparoscopy was increased by 14-fold for patients with cancer, 4. 5-fold for patients with benign disease, and 12-fold for patients with adnexal masses. No change in the mean LOS of nonsurgical admissions was noted, yet overall LOS for all patients decreased from 6.3 to 4.8 days (P < 0.0001). Mean LOS in surgical patients decreased from 9.4 to 6.0 days (P < 0.0001). After correction for complications, decreases in LOS only occurred in procedures for which laparoscopy was significantly integrated. No reductions in LOS were noted with like surgical approaches; i.e., there was no change in the LOS of patients undergoing laparotomy in both years. Surgical complications were not increased by laparoscopy. CONCLUSIONS: Aggressive utilization of operative laparoscopy, even only for selected patients, into the surgical practice of a gynecologic oncology service demonstrates significant improvements in LOS without adversely affecting surgical complication rates.

Use of the umbilicus in reconstruction of the vulva and vagina with a rectus abdominis musculocutaneous flap.

Flap reconstruction of the vulva and vagina following gynecological ablative procedures has become an integral part of the management of gynecological oncology patients. The benefits of flap reconstruction, including early primary healing, improved cosmesis over skin grafting, and prolonged secondary wound healing, have been well accepted. Additionally, the creation of a neovagina or neovulva often restores the sexual function and positive body image of the patient lost to radical procedures. The gracilis musculocutaneous flap has been used extensively in flap reconstruction but reports of partial flap necrosis and the need for extensive dissection of both thighs have led to alternative flap choices. The rectus musculocutaneous flap, with its hardier cutaneous blood supply, is often too bulky and difficult to inset delicately around the preserved urethral and vaginal cuff. The umbilicus has the required soft tissue, and its conically contoured depression allows for delicate insetting of the rectus abdominis musculocutaneous flap around the urethral cuff. We present 2 patients who underwent vertical rectus musculocutaneous flaps with umbilical soft tissue to restore urinary function and to create a cosmetic nonfunctional vagina.

Morphometric and electron-microscopic analyses of the effects of gonadotropin-releasing hormone agonists on uterine leiomyomas.

OBJECTIVE: Reports on the histologic effects of gonadotropin-releasing hormone agonists on uterine leiomyomas provide conflicting results. Most previous studies used qualitative methods of analysis. Using quantitative and semiquantitative stereologic methods of analysis, we assessed volume density of hyalinized areas, cell density, nuclear volume, and cytoplasmic cross-sectional areas of smooth muscle cells in histologic sections and also measured diameters of collagen fibrils in electron micrographs of uterine leiomyomas. DESIGN: Thirty leiomyomas from patients treated with gonadotropin-releasing hormone agonists (10 different patient samples), age-matched control patients (10 different patient samples), and postmenopausal women (10 different patient samples) were used. Hyalinization was assessed using a microscope with a projection head and affixed morphometric grid. Cell size and density were evaluated using a video-based, computerized system attached to the microscope, for which morphometric ad hoc programs were written. Diameters of collagen fibrils were measured from electron micrographs. SETTING: The study was conducted in the Department of Pathology, Mount Sinai Medical Center, New York, NY. PATIENTS: A total of 30 patient samples were studied, with three groups comprising 10 samples each, including patients treated with gonadotropin-releasing hormone agonists, age-matched control patients, and postmenopausal women. RESULTS: Myomas from patients treated with gonadotropin-releasing hormone agonists exhibited more hyalinization, greater cell density, slightly smaller cell sizes, and larger collagen fibrils than those of age-matched control patients and postmenopausal women. CONCLUSIONS: Shrinkage after treatment with gonadotropin-releasing hormone agonists is attributed to smaller cell size and increased collagenization in myomas.

Cytology of sex cord tumor with annular tubules: a case report.

The cytologic findings of a sex cord tumor with annular tubules (SCTAT) that ruptured during laparoscopy are described. Features useful in distinguishing SCTAT from other ovarian sex cord tumors include the presence of highly cellular tubular formations containing well-delimited glassy pink material and absence of single cells. To the best of our knowledge, the cytology of SCTAT has not been previously reported.

A new technique for performing Syed-Neblett template interstitial implants for gynecologic malignancies using transrectal-ultrasound guidance.

PURPOSE: Interstitial brachytherapy plays an important role in the treatment of advanced and recurrent gynecologic malignancies. Unfortunately, the inability to visualize the tumor and surrounding normal structures during the implant has hampered the accuracy and safety of the implant. Transrectal ultrasound guided Syed-Neblett template implantation is a new technique for performing interstitial implants under direct visualization. The details of the technique are presented to demonstrate the ability to accurately guide needle placement into tumor and avoid needle insertion into critical surrounding normal structures. METHODS AND MATERIALS: The transrectal ultrasound is positioned so that it can visualize the tumor, and normal surrounding structures in both transverse and longitudinal planes. The Syed-Neblett template is positioned and sutured into the perineum. Needles are inserted into the target area under direct visualization through transverse imaging. The bladder and rectum can be directly imaged and thus avoided. Longitudinal imaging is then used to guide the needles to the appropriate depth. In addition, it can be used to assess the length of the target volume and aid in determining the active length of the sources. RESULTS: A total of 12 procedures have been performed on seven patients from August 30, 1995 to April 12, 1996. The presenting diseases included: Stage IIIb cervical cancer in four cases, recurrent endometrial cancer in two cases, and Stage III vaginal cancer in one case. The total length of time for implantation of the needles ranged from 45 to 165 min (median--130 min). CONCLUSION: Transrectal ultrasound guidance provides real-time visualization of the target volume and normal tissues during interstitial implantation of gynecologic malignancies and allows for accurate needle placement.

Enhanced radiosensitization with interferon-alpha-2b and cisplatin in the treatment of locally advanced cervical carcinoma.

PURPOSE: To evaluate the efficacy and toxicity of interferon-alpha-2b (IFN-alpha) and cisplatin given concomitantly with radiation therapy (RT) in the treatment of locally advanced cervical carcinoma. MATERIALS AND METHODS: Twenty-one patients with stage bulky Ib-IIIb (Ib, 2; IIa, 2; IIb, 8; IIIb, 9) cervical carcinoma were treated with combined IFN-alpha (5 million IU) subcutaneously three times per week and cisplatin (25 mg/m2) i.v. infusion over 2 h weekly for 7 weeks, given concomitantly with RT (4500 cGy of external beam plus 2 brachytherapy procedures). Total radiation doses delivered ranged from 7500 to 9960 cGy (median, 9300 cGy). Follow-up ranged from 16 to 33 months (median, 25 months). RESULTS: The 2-year local control rate was 100%. The only sites of disease recurrence were distant. Freedom from distant metastases, disease-free survival, and overall survival at 2 years was 76%. Late complication rates were high. Grade 4 rectosigmoid, bladder, and small bowel complication rates were 49, 18, and 23% at 2 years. Late toxicity was seen earlier than expected with rectosigmoid complications observed 5 to 11.5 months (median, 8 months) after completion of treatment. CONCLUSION: Combination IFN-alpha and cisplatin produced a marked effect of enhanced radiosensitization as evidenced by 100% local tumor control and high late normal tissue complication rates. Due to the unacceptable late toxicity, its routine clinical use cannot be recommended. Further investigation is needed to determine whether a therapeutic window exists such that the use of lower doses of IFN-alpha, cisplatin, or RT can increase tumor control with more acceptable normal tissue toxicity.

Screening for human immunodeficiency virus in inner city females with abnormal cervical cytology.

OBJECTIVE: This report evaluates the acceptance, results, and predictors of human immunodeficiency virus (HIV) infection in inner city women referred to a colposcopy clinic for abnormal cervical cytology. METHODS: HIV testing results of 1,908 inner city women referred for abnormal cervical cytology were analyzed retrospectively with respect to acceptance, race, ethnicity, Pap smear results, sexually transmitted diseases (STDs), HIV exposures, and final histologic findings. RESULTS: HIV testing was accepted by 50.4% of patients. Women who agreed to screening were significantly more likely to admit exposure to HIV or to be Hispanic, foreign-born, or have a history of multiple STDs. Of those screened, 3.3% were found to be HIV seropositive. Although higher grades of referral Pap smears were noted in the women found to be HIV seropositive, final histologic findings were not different. The only predictors of unknown HIV seropositivity were admitted HIV exposure and external condyloma. CONCLUSIONS: Fifty percent of inner city women of unknown HIV status referred for abnormal cervical cytology will accept HIV serotesting and 3.3% are found to be positive. Most HIV-seropositive women can be detected based on either a history of exposure to HIV or the presence of external condyloma.

Pelvic exenteration in gynecologic oncology: Experience at the Mount Sinai Center, 1975-1992.

Thirty-nine patients underwent pelvic exenteration for gynecologic malignancies at The Mount Sinai Medical Center between 1975 and 1992. Surgical techniques, morbidity, survival, and other variables for patients so treated in two periods, 1975-1984 and 1985-1992, were compared. The primary cancer included squamous cell carcinoma of the cervix, 27; adenocarcinoma of the cervix, 1; squamous cell carcinoma of the vagina, 4; adenocarcinoma of the endometrium, 4; squamous cell carcinoma of the vulva, 2; and adenocarcinoma of the rectum, 1. Median survival was 23.1 months, with a median follow-up of 18 months. Survival was significantly related to status of the lymph nodes (p 0.0004) and surgical margins (p 0.0038). There were two postoperative mortalities, one due to pulmonary embolus and another to myocardial infarction. The ability in the second period analyzed, 1985-1992, to integrate a continent urinary reservoir and supralevator exenteration without colostomy yet not induce increased morbidity or decreased survival, has not been previously reported.

Manchester procedure vs. vaginal hysterectomy for uterine prolapse. A comparison.

The Manchester procedure (MP) was compared with vaginal hysterectomy (VH) to determine whether any differences regarding patient demographics or operative or postoperative outcome could be found between the two techniques. A retrospective chart analysis was done comparing data from 88 consecutive MP to 105 randomly selected VH patients. All the operations were performed for uterine prolapse at Mount Sinai Hospital between 1984 and 1988. MP patients, when compared to VH patients, were more likely to be older and postmenopausal at the time of surgery and to have a private physician. MP patients were less likely to have significant medical illnesses than were VH patients. Statistically significant differences between MP and VH were found for operative time (100 vs 130 minutes, respectively) and blood loss (200 vs. 300 mL, respectively) (P < .001). This difference was not dependent on the performance of anterior or posterior repair. MP was associated with shorter operative time and less blood loss when compared to VH. This, coupled with apparently similar operative outcomes, suggests the use of MP as an alternative to VH in the absence of uterine pathology in appropriate candidates with uterine prolapse. Prospective, controlled, long-term studies comparing the operative results of these two procedures are needed.

The stapled continent ileocecal urinary reservoir in the surgical management of gynecologic malignancy.

Total cystectomy at the time of radical pelvic surgery for gynecologic malignancies is not uncommon. Many techniques have been developed for urinary diversion including the continent ileocecal urinary reservoir. Twenty-nine patients underwent construction of a continent ileocecal urinary reservoir during the reconstructive phase of an exenterative procedure or for the relief of urinary tract fistula between 1990 and 1993. All procedures were performed using the mechanical stapling devices using metal staples. The right and proximal transverse colon were mobilized to a length of 24 cm. The ileum was divided 8 cm proximal to the ileocecal valve and plicated using the stapling technique. The colonic segment was opened on its antimesenteric border and the reservoir was created by stapling in a fashion to reapproximate the distal ends to each other. The ureters were stented and implanted without tunneling. A large Malecot drain was placed in all the pouches for irrigation of the colonic mucosa in the postoperative period. The ileal stoma was fixed to the anterior abdominal wall as was the anterior surface of the pouch. Operative time ranged from 50 to 150 min for the pouch construction. All patients underwent retrograde contrast study of the pouch 7-10 days postoperatively to verify lack of anastomatic leaks. After recovery, all patients successfully self-catheterized the pouch three to five times daily without difficulty. Of the 29 patients, 17 (59%) had received prior radiation as part of therapy. All patients remained continent at the end of observation. One developed a fistula to the perineum after intraoperative placement of 125I seeds on the pelvic wall. One patient developed pouch stones; endoscopic evaluation of this pouch revealed no evidence of stones at the staple lines and metabolic workup demonstrated hypocitremia as the etiology for the stones. Mean reservoir volume was 550 ml. Mean follow-up is 15.8 months; 5 have expired due to recurrent disease and 19 (83%) remain alive. Only two patients have been admitted for urosepsis due to reflux pyelonephritis. The stapled continent ileocecal reservoir offers benefits to patients undergoing total cystectomy. Using the mechanical stapling devices decreases the operative time and has not resulted in stone formation or pouch leakage. The complications of the procedure are acceptable.

Growth factor expression in normal peritoneum of patients with gynecologic carcinoma.

Both epidermal growth factor receptor (EGFR) and HER-2/neu (neu) have been found to be of prognostic importance in epithelial ovarian and endometrial carcinoma, but alterations in proto-oncogene expression of normal tissues of patients with gynecologic malignancies are unknown. Patients (118) undergoing laparotomy for gynecologic indications (78 ovarian cancer, 11 endometrial cancer, 19 benign gynecologic disease, 10 other cancers) had biopsies of normal peritoneum for quantitative assessment of neu and EGFR concentrations. Patients undergoing exploration for gynecologic malignancy were found to have significantly higher median neu expression in the peritoneal biopsies than patients with benign gynecologic disease (P = 0.002). Most patients in this study were found to have ovarian cancer, and median peritoneal neu expression was found to be significantly higher in patients with ovarian cancer versus benign ovarian masses (P = 0.0008) or any benign gynecologic disease (P = 0.004). No significant alteration of unbound EGFR was found in peritoneal biopsies of any of the groups of patients. No associations were found for a history of breast cancer, presence of ascites, or menopausal status with alteration of neu or EGFR expression in normal peritoneum. These findings of altered expression of neu in normal tissues of patients with ovarian cancer are suggestive of the presence of proto-oncogene alterations in loco-regional tissues of the peritoneum, such as might be seen if a paracrine influence existed between tumor and peritoneal cells. Alternatively, the alterations may represent subtle alterations of proto-oncogene expression of germ-line tissues.