Positive Peritoneal Washing Cytology Research Articles

Pilot study of adjuvant hyperthermic intraperitoneal chemotherapy in patients with colorectal cancer at high risk for the development of peritoneal metastases

The prognosis of peritoneal metastases from colorectal cancer has recently improved with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Although outcomes are further improved when early stage peritoneal metastases are treated, adjuvant hyperthermic intraperitoneal chemotherapy has never been thoroughly addressed. This prospective pilot study assessed feasibility, safety and efficacy of hyperthermic intraperitoneal chemotherapy combined with primary curative surgery in colorectal cancer at high risk for peritoneal metastases. Twelve patients were prospectively selected according to predetermined risk factors for the development of peritoneal metastases. Patients underwent conventional colon surgery, closed-abdomen mitomycin-C plus cisplatin-based hyperthermic intraperitoneal chemotherapy, and cytoreductive surgical procedures, as needed. Preoperative tumor-related risk factors were confirmed by intraoperative findings and pathological examination in all patients: minimal synchronous peritoneal metastases (n = 2), synchronous ovarian metastases (n = 1), positive peritoneal washing cytology (n = 2), primary tumor directly invading other organs (n = 6), or penetrating visceral peritoneum (n = 1). Major morbidity occurred in 2 patients and operative death in none. Median follow-up was 49 months (range, 22-72). Peritoneal metastases occurred in 1 patient and distant metastases in 2. Five-year overall survival was 83.3%. Preoperative/early intraoperative assessment can reliably identify colorectal cancer patients at high risk for peritoneal metastases. Adjuvant hyperthermic intraperitoneal chemotherapy is well tolerated and safe. These preliminary results would support the design of future phase-III trials of adjuvant hyperthermic intraperitoneal chemotherapy.

Positive peritoneal washing cytology is a potential risk factor for the recurrence of curatively resected colorectal cancer

Whether free peritoneal cancer cells should be considered peritoneal dissemination in colorectal cancer patients remains controversial. The aim of this study was to investigate the clinical significance of positive peritoneal washing cytology (PWC) in patients with colorectal cancer. We retrospectively analyzed the records of 771 sequential patients diagnosed with stage 0-III colorectal cancer who underwent R0 resection and had no distant metastases or peritoneal dissemination. PWC was performed on all 771 patients. Sixty-eight patients experienced metastasis recurrence, 10 of whom experienced peritoneal recurrence. Of the 10 patients with peritoneal recurrence, 6 had positive PWC. Out of the 771 patients, 21 had positive PWC. Of these 21 patients, 6 had peritoneal recurrence, while 4 had distant metastasis and no peritoneal recurrence during the observation period. The 5-year disease-free survival was 89.0 % in the patients with negative PWC vs. 46.8 % in the patients with positive PWC (p < 0.0001, log-rank test). A Cox proportional hazards model revealed that positive PWC was the strongest independent risk factor for cancer-specific recurrence. Our study highlights PWC as a useful prognostic tool in patients undergoing curative surgery for colorectal cancer, since positive PWC was shown to be a potential risk factor for recurrence.

Abstract 1473: Epithelial to mesenchymal transition predicts prognosis In clinical gastric cancer.

Abstract Background; Epithelial-to-mesenchymal transition (EMT) is thought to play an important role in cancer invasion and metastasis and could be a critical target to improve survival. Recently, EMT has been actively studied in various cancers. In this study, we explored the impact of EMT on clinical prognosis of gastric cancer. Methods; Eleven gastric cancer cell lines (N87, NUGC2, MKN45, NUGC4, KATOIII, MKN74, SC-6-JCK, GCIY, MKN28, AZ521 and MKN1) and one hundred sixteen patients who underwent surgery for gastric cancer in our hospital were investigated in this study. The mRNA expression level of an epithelial marker (E-cadherin), a mesenchymal marker (vimentin) and several transcription factors known to induce EMT were measured by quantitative real-time PCR. EMT status of each gastric cancer patient was determined by calculating the V/E ratio (vimentin mRNA expression divided by E-cadherin expression in cancerous tissues) and the correlation between EMT status and clinicopathological factors and prognosis were analyzed. Results; 86 patients were classified as having epithelial tumors and 30 patients as having mesenchymal tumors. Mesenchymal tumor type was significantly associated with pathological diffuse type cancer (P = 0.0002) and stage IV (P = 0.046). On multivariate analysis, tumor size (≧ 65mm) (P = 0.013), T classification (T3/4) (P = 0.020), positive peritoneal washing cytology or peritoneal metastasis (P = 0.0002) and EMT status (mesenchymal phenotype) (P = 0.043) were independent prognostic factors for gastric cancer patients. Seven of the gastric cancer cell lines were classified as epithelial and four were classified as mesenchymal. Among the five transcription factors (Twist, Slug, Snail, Zeb-1 and Zeb-2) analyzed, Zeb-1 mRNA expression was significantly correlated with mesenchymal phenotype and the V/E ratio (r = 0.708, P = 0.015). These results indicated that Zeb-1 could play a key role in EMT for gastric cancer cell lines. Zeb-1 mRNA expression was therefore measured by real-time PCR in cancerous tissues from patients, and the patients were divided into low (n =84) and high (n = 32) expression groups. Not surprisingly, we found a significant correlation between V/E ratio and Zeb-1 mRNA expression (r = 0.727, P &amp;lt; 0.0001). High Zeb-1 expression was also significantly associated with age ( 63), pathological diffuse type and number of lymph node metastasis (n ≧ 16), (P = 0.036, P = 0.035, P = 0.018, respectively). Finally, patients in the high-expression group had significantly poorer survival than those in the low-expression group (P = 0.0071). Conclusion; EMT is a critical prognostic factor for gastric cancer. Zeb-1 is an important EMT-inducing transcription factor and might be a therapeutic target for patients with gastric cancer. Citation Format: Toshifumi Murai, Suguru Yamada, Bryan C. Fuchs, Tutomu Fujii, Michitaka Fujiwara, Kenneth K. Tanabe, Yasuhiro Kodera. Epithelial to mesenchymal transition predicts prognosis In clinical gastric cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1473. doi:10.1158/1538-7445.AM2013-1473

Peritoneal washing cytology in an adult granulosa cell tumor: A case report and review of literature

Adult-type granulosa cell tumors (AGCT) account for 1-2% of all ovarian tumors and 95% of granulosa cell tumors. In AGCT, at the time of peritoneal washing, tumor cells are rarely seen to exfoliate and FIGO stage is raised from IA/IB or IIA/IIB to stage IC or IIC despite the absence of a gross intraepithelial tumor. Patients with positive peritoneal washing cytology must be followed up for pelvic recurrence and metastasis. A more sensitive cytologic evaluation, histopathologic correlation and immunohistochemical staining can advance our practice. Here, we describe a case of AGCT with the emphasis on cytologic features observed in specimens obtained from peritoneal washing fluid.

Phase II study of weekly intravenous and intraperitoneal paclitaxel combined with oral S-1 for advanced gastric cancer with macroscopic peritoneal metastasis.

e14530 Background: This phase II study was performed to evaluate the efficacy and the tolerability of weekly intravenous and intraperitoneal paclitaxel (PTX) combined with oral S-1 in gastric cancer patients with macroscopic peritoneal metastasis. We previously reported a phase I and II study with the same regimen in gastric cancer patients with peritoneal metastasis, including patients with positive peritoneal washing cytology but negative macroscopic peritoneal metastasis. This trial was scrutinized and approved by a committee appointed by the Ministry of Health, Labour, and Welfare in Japan and performed under the special interim system for Advanced Medical Technology so as to generate an evidence for future approval of the treatment by the Ministry. Methods: Gastric cancer patients with primary tumors with macroscopic peritoneal metastasis confirmed by staging laparoscopy were enrolled. PTX was administered intravenously at 50 mg/m2, and intraperitoneally through a subcutaneous implanted access port at 20 mg/m2 on days 1 and 8. S-1 was administered orally twice daily at 80 mg/m2/day for 14 consecutive days followed by 7 days rest, repeated every 3 weeks. The primary endpoint was the one-year overall survival rate. Secondary endpoints were the response rate, efficacy against malignant ascites and safety. Results: In total, 35 patients were enrolled. All patients had several to numerous metastases to the distant peritoneum. The median number of administration course was 11 (range 2-29). The one-year overall survival rate was 77.1%. Massive malignant ascites decreased in 6 of 9 (66.7%) patients. Peritoneal washing cytology turned negative in 28 of 29 (96.7%) patients. The incidences of grade 3/4 hematological and non-hematological toxicities were 34% and 9%, respectively, all of which were reversible. Grade 3/4 toxicity was observed for neutropenia (34%), leukopenia (23%), anemia (9%). There were no treatment-related deaths. Conclusions: The combination chemotherapy regimen of weekly intravenous and intraperitoneal PTX combined with oral S-1 was well tolerated and active in gastric cancer patients with macroscopic peritoneal metastasis.

Peritoneal washing cytology in patients with BRCA1 or BRCA2 mutations undergoing risk-reducing salpingo-oophorectomies: A 10-year experience and reappraisal of its clinical utility

ObjectiveTo evaluate the utility of peritoneal washing cytology (PWC) for detecting occult primary peritoneal carcinoma in patients with BRCA1 or BRCA2 mutations, we reviewed PWCs obtained during risk-reducing salpingo-oophorectomy (RRSO) from 117 patients at our institution and correlated the results with surgical pathology findings. MethodsRecords of 128 PWCs from 125 patients with BRCA1 or BRCA2 mutations undergoing RRSO at MD Anderson Cancer Center between 2000 and 2010 were obtained. Slides were available for review for 119 PWCs from 117 patients (2 patients had 2 PWCs each). Cytopathologists, blinded to the RRSO histopathologic diagnoses, categorized the PWCs as benign, atypical, suspicious for malignancy, or malignant. These results were correlated with the RRSO histopathologic diagnoses. ResultsPWCs from 113 patients were benign. Of the remaining 4 patients, 2 had PWCs classified as atypical, 1 as suspicious for malignancy, and 1 as malignant. The corresponding RRSO histopathologic findings of the 2 atypical PWCs showed endosalpingiosis and cystadenofibroma in one case and showed no abnormalities in the other case. Both patients with suspicious or malignant PWCs, indicating the possibility of occult peritoneal carcinoma, had RRSO histopathologic diagnoses of endometriosis and endosalpingiosis. Nine patients had abnormal tubal or ovarian histologic findings, but all 9 of these patients had benign PWCs. ConclusionPWC has the potential to detect occult peritoneal carcinoma in patients with BRCA1 or BRCA2 mutations. The clinical significance of a positive PWC without abnormal RRSO histology remains unclear and will require long-term follow-up for determination.

The Role of Pelvic and/or Para-Aortic Lymphadenectomy in Surgical Management of Apparently Early Carcinosarcoma of Uterus

To determine the incidence of lymph node (LN) metastasis in patients with apparently early carcinosarcoma of the uterus, to analyze the clinicopathologic factors associated with LN metastasis, and to evaluate the role of pelvic and/or para-aortic lymphadenectomy in treatment of such conditions. We retrospectively analyzed 41 patients with carcinosarcoma intraoperatively confined to the uterus who underwent complete staging procedures including pelvic and/or para-aortic lymphadenectomy. After surgery, two patients (4.9%) were upstaged to stage IIIA because of positive peritoneal washing cytology, and 13 (31.7%) were upstaged to stage IIIC as a result of LN metastasis. Five patients had pelvic, three had paraaortic, and five had both pelvic and para-aortic LN metastases. The mean number of metastatic LNs was 3.7 (range 1-15). On multivariate analysis, myometrial invasion >1/2 [odds ratio (OR) 8.50; 95% confidence interval (CI) 1.57-45.92; P = 0.013] and lymphovascular space invasion (LVSI) (OR 8.50; 95% CI 1.57-45.92; P = 0.013) were significantly predictive of LN metastasis. After a median follow-up interval of 32 months (range 3-179 months), the 2-year disease-free survival (DFS) and overall survival (OS) rates were 73% and 84%, respectively, and the 5-year DFS and OS rates were 73% and 69%, respectively. Patients with LVSI or LN metastasis had significantly poorer DFS and OS. Pelvic and para-aortic lymphadenectomy should be performed in patients with apparently early carcinosarcoma of the uterus, especially in those with myometrial invasion >1/2 or LVSI.

Positive Peritoneal Washing Cytology in Multiple Cavities Can Predict Poor Prognosis of Advanced Gastric Cancer Patients

Positive peritoneal washing cytology (PWC) has been reported to be a poor prognostic factor for gastric cancer. Japanese gastric cancer classifications recommend PWC in Douglas' pouch for advanced gastric cancer. However, the sensitivity of PWC is relatively low. The goal of this study was to investigate whether PWC in multiple cavities increases its sensitivity to predict prognosis. Between January 1996 and December 2006, a series of 992 patients with gastric cancer underwent D2 gastrectomy with intraoperative PWC. Of the 992 patients, 62 patients had positive PWC. PWC was conducted in four cavities (left subphrenic cavity, right subhepatic cavity, Douglas' pouch, and inside the omental bursa). The 62 patients were retrospectively analyzed for their background and survival. Eleven (17.7%) patients had negative PWC in Douglas' pouch but were positive in the other cavities. The 62 patients were classified into two groups according to the number of positive PWC cavities: 20 patients with one or two and 42 patients with three or four positive PWC cavities. No significant difference in clinicopathological features was observed between these two groups. However, the overall and progression-free survival rates of patients with one or two positive PWC cavities were significantly higher than those for patients with three or more positive PWC cavities. PWC in multiple cavities was more sensitive than only in one cavity. The number of positive cavities may indicate the grade of tumor spread in the peritoneum and predict the prognosis of patients with positive PWC.

Preoperative Serum CA-125 Levels in Endometrial Cancer

In Brief Objective: The aim of this study was to evaluate properative serum levels of CA-125 for the prediction of advanced stages of endometrial cancer. Method: Retrospective study evaluated 114 women with pathologically proven endometrial carcinoma treated in our institution that had preoperative serum CA-125 levels between January 1990 and December 2005. The association of preoperative serum CA-125 with a different histopathologic factors was evaluated. Statistical analysis was performed using Mann-Whitney U test and Kruskal-Wallis test and a logistic regression. Results: Elevated serum CA-125 levels were significantly correlated with advanced-stage disease, lymph node metastases, increased depth of myometrial invasion (P < 0,01). Similar correlation was seen between levels of CA-125 and positive peritoneal washing cytology, distant metastases and highest histologic grade. Multivariate analyses using logistic regression showed that lymph node metastases had the most significant effect on the elevation of preoperative serum CA-125 levels. Conclusion: The preoperative serum CA-125 level appears to be a significant independent predictor of advanced-stage disease and lymph node metastasis. Therefore, preoperative serum CA-125 may be a useful tool, in the clinical setting, for optimal individualized patient management. A CA-125 level should be included as a part of the preoperative workup for all patients with endometrial cancer. Preoperative serum CA-125 may be a useful tool, in the preoperative workup for all patients with endometrial cancer.

Peritoneal cytology in colorectal cancer: incidence and prognostic value

Background The value of peritoneal washing cytology on prognosis is not clear yet. The aims of our prospective study were to consider the incidence and prognostic value of peritoneal cytology. Methods From 1996 to 2003, washing cytology was performed in 88 patients who underwent surgery for colorectal cancer. Before exploration and manipulation of the tumor, each of the peritoneal cavities next to the tumor site, subhepatic and rectovesical recesses, were irrigated with 50 mL saline, and then the aspirates were taken for cytological evaluation. Results Thirteen (14.7%) of 88 patients had positive cytology. Although necrosis, depth of invasion, differentiation of the tumor, macroscopic peritoneal dissemination, and ascites were correlated with positive cytology; multivariate analyses revealed the depth of invasion, presence of necrosis, and differentiation of the tumor as the factors affecting the cytology. The disease-free and overall-survival times in patients with positive and negative peritoneal washing cytology were 56.36, 61.40 and 52.08, 63.94 months, respectively ( P > .05). Conclusion The presence of free malignant cells in the peritoneal cavities of patients who underwent curative resection for colorectal cancer provides no further prognostic value over the current staging systems.

Prognostic significance of peritoneal washing cytology in Thai patients with gastric adenocarcinoma undergoing curative D2 gastrectomy

The aim of the present study was to determine the prognostic significance of peritoneal washing cytology (PWC) among Thai patients with gastric adenocarcinoma. Medical charts of 97 patients with gastric adenocarcinoma who underwent curative D2 gastrectomy between October 1995 and September 2005 were reviewed. A total of 22 patients (23%) had positive PWC. Factors significantly associated with positive PWC included tumor location, macroscopic findings, histology, depth of tumor invasion, nodal involvement, TNM stage, and angiolymphatic invasion. Positive PWC was found only in tumors invading the serosa. All patients with positive PWC developed peritoneal recurrence. The sensitivity and specificity of positive PWC in predicting peritoneal recurrence were 61% and 100%, respectively. The overall 5-year survival rates for patients with positive and negative PWC were 0% and 75%, respectively. Gastric adenocarcinoma with positive PWC should be considered stage IV disease. PWC should be included in the staging of gastric adenocarcinoma.

Analysis of Methylated Genes in Peritoneal Fluids of Ovarian Cancer Patients: A New Prognostic Tool

Epithelial ovarian cancer causes more deaths in the United States and Europe than any other cancer of the female reproductive organs. The latest cancer statistics indicated an estimated 25 400 new cases of ovarian cancer and 14 300 deaths in the United States (1). The primary treatment for early-stage ovarian cancer is surgery, which in theory could be curative in low-risk patients whose disease is limited to the ovaries. The relative importance of prognostic factors such as tumor grade, histologic cell type, and other factors for defining individuals at low risk of recurrence is unknown (2). Cytologic examination of peritoneal fluids forms part of the staging process for ovarian cancer and influences therapeutic interventions (3). It is known that regardless of International Federation of Gynecology and Obstetrics (FIGO) stage, positive peritoneal washing cytology predicts poor prognosis for women with epithelial tumors of the genital tract, except for patients with borderline ovarian tumors (4). Because of the diagnostic pitfalls entailed in the cytologic examination of peritoneal washings (5), some additional methods for peritoneal fluid diagnosis have been tested, including flow cytometric DNA analysis (6) and a telomerase assay (7)(8). Changes in the status of DNA methylation, known as epigenetic alterations, are among the most common molecular alterations in human neoplasia (9)(10), including ovarian cancer (11)(12)(13). Moreover, it is now widely known that methylated DNA can be detected in various body fluids and that the methylation status of some genes can be used for risk assessment of various types of human neoplasia [summarized in Ref. (14 …

Implications of peritoneal washing cytology in patients with potentially resectable pancreatic cancer.

The aim of this study was to assess the implications of positive peritoneal washing cytology for management of patients with potentially resectable pancreatic cancer. Cytological examination of peritoneal washings was performed in 134 patients who underwent surgical resection for pancreatic adenocarcinoma. The clinicopathological findings and the relationship between cytology results (including cytomorphology) and survival were investigated. One hundred and fourteen patients (85 per cent) had negative cytology results (group 1). Excluding one patient with atypical cells, positive cytology results were obtained in 19 patients (14 per cent): 16 patients without macroscopic peritoneal metastases (group 2) and three patients with minimal macroscopic peritoneal metastases (group 3). The patients in group 2 had significantly larger (P < 0.001) and more advanced (P = 0.022) tumours than those in group 1. However, there were no significant differences in postoperative cumulative survival rates between groups 1 and 2 (P = 0.347). Two patients in group 2 are long-term survivors (40 and 58 months). In cytomorphological analyses, the presence of clusters with ragged edges and isolated carcinoma cells can be considered to indicate a high risk of peritoneal recurrence. Positive cytology does not directly predict peritoneal carcinomatosis and, while associated with advanced disease, does not contraindicate radical surgery.

Peritoneal Washing Cytology on Fluid Hysteroscopy and After Curettage in Women with Endometrial Carcinoma

To assess the influence of fluid hysteroscopy with target biopsy of the endometrium and the influence of added curettage on the results of peritoneal washing cytology (PWC) in endometrial carcinoma. In 42 women at risk of endometrial carcinoma, we performed fluid hysteroscopy with target biopsy of the endometrium and curettage. Evaluation of PWC of the pouch of Douglas was performed three times during the procedure: prior to hysteroscopy, after fluid hysteroscopy with target biopsy and after curettage. On cytologic slides from peritoneal washings in 11 patients with carcinoma of the endometrium, malignant endometrial cells were found after curettage in 72.7%. There was no statistically significant difference in PWC prior to hysteroscopy (two women, 20%) or after hysteroscopy with target biopsy (three women, 30%). There was a statistically significant difference (.05 level) in positive PWC after hysteroscopy with target biopsy (three women, 33.3%) and after curettage (eight women, 88.9%). Slides from carcinoma of the endometrium in PWC do not deteriorate after hysteroscopy with target biopsy of the endometrium, but tumor cells will appear in the pouch of Douglas after curettage.

Peritoneal Washing Cytology in Gynecologic Cancers: Long-term Follow-up of 355 Patients

Microscopic evaluation of cells washed from the peritoneal cavity during surgery for gynecologic tumors is used to detect subclinical intraperitoneal metastases from these tumors. The prognostic significance of this test, however, has been questioned. Stressing histologic correlation and pitfalls in interpretation, we previously reported that the sensitivity of intraoperative peritoneal washing cytology was lower than was suggested earlier. This study evaluates the clinical utility of this test in the long-term follow-up of our patients. Staging (International Federation of Gynecology and Obstetrics [FIGO], 1971) and follow-up information was available for 355 unselected patients with primary tumors who had peritoneal washings performed during initial surgery at University Hospital-Stony Brook, NY, during the period from 1980 through 1989. There were 135 patients with endometrial carcinomas, 112 with ovarian carcinomas, 92 with cervical carcinomas, and 16 with borderline (i.e., of low malignant potential) ovarian tumors. The median follow-up of the patients was 57 months (range, 0-154 months). Follow-up data were obtained from the Tumor Registry at University Hospital-Stony Brook. Survival differences were determined by Kaplan-Meier analysis and were evaluated by two-tailed logrank test. RESULTS. Peritoneal washing cytology was positive at initial surgery for 120 (33.8%) of 355 patients, including 90 (80.4%) of 112 patients with ovarian carcinomas, five (31.2%) of 16 patients with borderline ovarian tumors, 17 (12.6%) of 135 patients with endometrial carcinomas, and eight (8.7%) of 92 patients with cervical cancers. For 203 patients with stage I tumors, the peritoneal cytology was positive in 29.4% of the patients with ovarian carcinomas, 18.2% with borderline ovarian tumors, 6.1% with endometrial carcinomas, and 5.2% with cervical carcinomas. By use of peritoneal histology as the standard, peritoneal cytology was highly specific (98.1%) but less sensitive (82.9%) in detecting intraperitoneal involvement. For patients with stage I tumors, 80.0% with ovarian carcinomas, 83.3% with endometrial carcinomas, and 100% with cervical carcinomas who showed positive cytology died of their cancer, compared with 25.0% with ovarian carcinomas, 13.0% with endometrial carcinomas, and 21.9% with cervical carcinomas who showed negative peritoneal cytology. Four (2.0%) patients with stage I tumors had positive peritoneal cytology but negative peritoneal histology. Of these patients, three (two with ovarian carcinoma and one with cervical carcinoma) died of their cancer, whereas one patient with a borderline ovarian tumor was free of disease at the last follow-up. Survival analysis indicated that peritoneal washing cytology stratified for stage provides better prognostic information for each primary cancer site studied than does stage alone. All patients with borderline ovarian tumors were alive at last follow-up, regardless of disease stage or peritoneal status. Regardless of FIGO stage, positive peritoneal washing cytology predicted poor prognosis for women with epithelial tumors of the genital tract, except for patients with borderline ovarian tumors. Patients in whom peritoneal cytology was the only evidence of intraperitoneal spread were few, but the disease in such patients was associated with poor outcome. Strict adherence to specialized cytologic criteria in peritoneal washing cytology allows for results that are highly predictive of survival. This information may be useful in stratifying women in therapeutic trials for treatment of genital tract carcinomas.

Expression of epidermal growth factor family proteins and epidermal growth factor receptor in human endometrium

The biological significance of epidermal growth factor (EGF)—related proteins in the development and progression of endometrioid endometrial carcinoma was studied. Expression of EGF-related proteins including EGF, transforming growth factor-α (TGF-α), cripto (CR), amphiregulin (AR), and EGF receptor (EGFR) were immunohistochemically examined. Results were then correlated with clinicopathologic findings and steroid receptor status in 12 specimens with normal endometrium, 13 with endometrial hyperplasia, and 40 with endometrioid endometrial carcinoma. EGFR, EGF, TGF-α, and CR iinmunoreactivities were observed in 58.3%, 66.7%, 91.6%, and 66.7% of normal endometrial specimens; 100%, 15.4%, 100%, and 30.8% of endometrial hyperplasia specimens; and 67.5%, 32.5%, 65.0%, and 65.0% of endometrial carcinoma specimens, respectively. AR immunoreactivity was not observed in any of the normal, hyperplastic, or neoplastic endometrium. The presence or absence of EGFR or TGF-α in endometrial carcinoma correlated with surgical stage, depth of myometrial invasion, and findings from peritoneal washing cytology. EGF expression significantly correlated with the age of the patients and that of CR with surgical stage and peritoneal washing cytological findings. There was a significant correlation between EGFR and TGF-α expression, and between EGF and TGF-α. Coexpression of EGFR and TGF-α, EGFR and CR, and TGF-α and CR in carcinoma specimens significantly correlated with advanced surgical stage, deeper myometrial invasion, and positive peritoneal washing cytology. In normal as well as hyperplastic endometrium, endometrial glands immunohistochemically positive for TGF-α were generally positive for ER, but in poorly differentiated endometrial carcinoma, cells positive for TGF-α tended to be negative for ER. The results of the present study show that among EGF-related proteins, expression of TGF-α and CR seem to be associated with the progression of human endometrioid endometrial carcinoma. Additionally, expression of TGF-α became increasingly estrogen independent with increasing histological carcinoma grades.

Microscopic ovarian metastasis of the uterine cervical cancer

Six hundred forty-seven cases of carcinoma of the uterine cervix with FIGO stages Ib or more were initially treated with hysterectomy at Kyushu University Hospital from 1973 to 1987. In these, 597 cases could be pathologically reviewed for ovarian metastasis. In these 597 cases, 335 were stage Ib, 71 IIa, 185 IIb, and 6 IIIb. Only 3 (0.5%) of 597 showed ovarian metastasis. All 3 cases were stage IIb. None of stage Ib cancer cases had ovarian metastasis. One (0.19%) of 524 squamous cell carcinomas metastasized to the ovary, whereas 2 (5.5%) of 36 pure adenocarcinomas revealed ovarian metastasis. Interestingly, all ovarian metastatic lesions were microscopic in size and found in the ovarian hilus. As for the primary lesion, all cases with ovarian metastasis showed deep myometrial invasion, corpus invasion, and lymphatic permeation. Two cases showed pelvic lymph node metastases and positive peritoneal washing cytology. From the results of our study, it can be said that it is fairly safe to preserve the ovary at the time of radical operation in squamous cell carcinoma of the uterine cervix, but it may not be safe to preserve the ovary in pure adenocarcinoma of the uterine cervix.