BACKGROUND: The HER-2/neu proto-oncogene (also known as c-ErbB-2) encodes a 185 kD transmembrane glycoprotein with intrinsic tyrosine kinase activity. Many studies revealed the correlation between the aberrant overexpression of HER-2/neu oncogene and poor prognosis of the malignant tumors such as breast, stomach, colon, lung cancers. But the significance of HER-2/neu oncogene overexpression as a prognostic factor in ovarian cancer remains controversial. OBJECTIVE: The aims of this study were to assess the prevalence of HER-2/neu oncogene amplification by polymerase chain reaction(PCR) and to evaluate the prognostic significance of HER-2/neu oncogene overexpression in terms of chemo-responsiveness and survival rate. MATERIALS AND METHODS: This study included 32 patients with advanced ovarian cancers(24 epithelial ovarian cancers, 2 Brenner tumors, 2 malignant mixed miillerian tumors, 2 granulosa cell tumors, 1 struma ovarii, 1 Krukenberg tumor). All patients had underwent staging laparotomy, and postoperative adjuvant chemotherapy with platinum-based combination chemotherapy. PCR was performed using tissues preserved in liquid nitrogen at the time of debulking operation. Overexpression of HER-2/neu oncogene was defined as being equal to or greater than 1.5 a.u. We analyzed whether the HER-2/neu overexpression correlated with chemoresponsiveness and 5-year survival rate(5-YSR). RESULT: HER-2/neu oncogene amplification was present in all of the ovarian cancers(32/32). Significant overexpression[gene copy number(GCN) > or =1.5 a.u.] was present in 13 of 32 ovarian cancers(41%) and 12 of 24 epithelial ovarian cancers (50%). The clinical response rate to chemotherapy in high copy group(GCN > or = 1.5 a.u.) was 67%(8/12) and that of low copy group(GCN<1.5 a.u.) was 92%(11/12)(p>0.05). Pathologic response rate to chemotherapy was 0%(0/5) and 50%(3/6), respectively(p>0.05). 5-YSR was 8% in high copy group and 25% in low copy group, but this difference was not statistically significant(p=0.17). CONCLUSION: HER-2/neu overexpression might be a poor prognostic factor, but this difference was not definitely elucidated by satistical analytsis in this study. Larger scaled prospective randomized study is needed to define the prognostidc significance of the HER-2/neu overezpression in ovarian cancer.
Breast ; Brenner Tumor ; Chemotherapy, Adjuvant ; Colon ; Drug Therapy ; Drug Therapy, Combination* ; Glycoproteins ; Granulosa Cell Tumor ; Humans ; Laparotomy ; Lung Neoplasms ; Nitrogen ; Oncogenes* ; Ovarian Neoplasms* ; Polymerase Chain Reaction ; Prevalence ; Prognosis ; Protein-Tyrosine Kinases ; Proto-Oncogenes ; Stomach ; Struma Ovarii ; Survival Rate

p73, a first p53 relative, has been identified at chromosome 1p36, a region that is deleted in variety of human cancers. This protein shares strong homology with p53 protein, suggesting functional similarities with p53. Indeed, p73 can activate p53 downstream genes inducing apoptosis or growth arrest in tumor cells lacking p53. This phenomenon leads us to investigate the function of p73 in ovarian cancer because aberrant p53 was very frequently found in this cancer. We hypothesize that DNA damaging agents trigger p53 dependent apoptotic pathway through p73 instead of p53 in ovarian cancer having aberrant p53. We selected SKOV3 ovarian cancer cell line having no p53 gene and treated this cell line with cisplatin. After the treatment, we examined the transcriptional level of p73 and p21. Moreover, to identify whether the status of p53 influence to the function of p73, we performed same experiment after inserting adenovirus mediated p53(Avp53) into cell line. We detected significantly increased transcripts of p73 whcn treated with cisplatin. But treated with Avp53 or combined treatment with cisplatin, the transcriptional levels were not changed. These data suggest that overexpression of p73 may be important to trigger apoptotic pathway when the p53 gene is lost, but not so important in cells having normal p53.
Adenoviridae ; Apoptosis ; Cell Line* ; Cisplatin ; DNA ; Genes, p53 ; Genes, Tumor Suppressor ; Humans ; Ovarian Neoplasms*

Twenty six cases of borderline ovarian tumor(BOT) were treated between Jan. 1985 and Dec. 1997 at the Department of Obstetrics and Gynecology, Hanyang University. The clinical records were reviewed for all patients including histopathology, clinical features, and follow-up. The frequency of BOT was 12%(26/214) of epithelial ovarian malignancies, and patients with these tumors tend to present at a younger age(36 yrs) than those with invasive carcinomas. In terms of histologic type, mucinous type(21/26: 81%) were more prevalent than serous tumor(5/21: 19%) in this study. The positive rate of CA 125 was 20% in serous, and the positive rate of CA 19-9 was 24% in mucinous tumor. The size of mucinous was larger than that of serous tumors(17.1 cm vs 9,3 cm). Almost all of these tumor categorized as early stage(stage I: 96%), however, only one patient with serous tumor had advanced stage of disease(stage III: 4%), Therefore BOT tend to be diagnosed as earlier than invasive carcinoma. About 2/3 of patients were treated as conservative surgery(unilateral salpingooophorectomy or enuclation). Postoperative adjuvant chemotherapy was not given about half of cases(13/26). Median follow-up was 43 months and recurrent case was found only one in serous tumor, All patients in this study are still alive and free of disease except one, 5-year survival rate was 100%. But large number of study and long-term follow-up are needed to make a decision to treat and manage of BOT.
Chemotherapy, Adjuvant ; Female ; Follow-Up Studies ; Gynecology ; Humans ; Mucins ; Obstetrics ; Ovary* ; Survival Rate

This study was performed to assess the significance of plasma level and histochemical character of carcinoembryonic antigen(CEA) in early diagnosis and prognosis of ovarian tumor. Plasma level of CEA was measured using EIA method and immunohistochemical tissue staining of CEA was done using biotin-strepto avidin complex immunoperoxidase technique. The percentage of patients with positive CEA level(above 2.5 ng/ml) was 23.1%(6/26) in malignant ovarian tumor and 15.6%(12/77) in benign ovarian tumor. Positive tissue staining of CEA was 42.3%(11/26) in malignant ovarian tumor and 19.5%(15/77) in benign ovarian tumor. In histologic typing, positive tissue staining of CEA was 18.1%(2/11) in serous cystadenocarcinoma, 85.7%(6/7) in mucinous cystadenocarcinoma, 37.5%(3/8) in other malignant ovarian tumors, 7.1%(1/15) in serous cystadenoma, 7.1%(1/14) in mucinous cystadenoma and 27.1%(13/48) in other benign ovarian tumors. Among 5 cases of malignant ovarian tumors with positive CEA level, 3 cases(60%) showed positive tissue staining of CEA, whereas among 21 cases of malignant ovarian tumors with negative CEA level, 8 cases (38.1%) showed positive tissue staining of CEA. However, among 11 cases of benign ovarian tumors with positive CEA level, 4 cases(36.4%) showed positive tissue staining of CEA, whereas among 66 cases of benign ovarian tumors with negative CEA level, 11 cases(16.7%) showed positive tissue staining of CEA. In the 3 year follow-up study of 12 cases with malignant ovarian tumor, among 3 cases with positive tissue staining of CEA, 2 cases(66.7%) survived. In 9 cases with negative tissue staining of CEA, 6 cases(66.7%) survived. In conclusion, these results suggest that the measurement of tumor CEA may be of value in the differential diagnosis of malignant and benign ovarian tumor, especially in diagnosing mucinous cystadenocarcinoma. However, due to the small amount of cases available for study, it was difficult to determine the correlation between the prognosis and tissue CEA staining of ovarian tumors.
Avidin ; Carcinoembryonic Antigen* ; Cystadenocarcinoma, Mucinous ; Cystadenocarcinoma, Serous ; Cystadenoma, Mucinous ; Cystadenoma, Serous ; Diagnosis, Differential ; Early Diagnosis ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Plasma* ; Prognosis

c-erbB-2 oncogene is a gene that encodes a growth factor receptor-like molecule with tyrosine kinase activity and has a structure similar to that of the epidermal growth factor receptor. Overexpression of the c-erbB-2 oncoprotein is detected in human adenocarcinoma of the breast, cervix, and salivary gland, in all of which the association between overexpression of the c-erbB-2 and poor prognosis of the disease has been reported. The role of c-erbB-2 oncoprotein in the tumorigenesis of the human ovary has been poorly understood and remains controversial. In order to explore the relationship between c-erbB-2 oncoprotein status and ovarian carcinoma, tissue from 32 patients, each of whom had invasive ovarian carcinoma prior to treatment, 10 patients with benign cyst and 10 control case who underwent hysterectomy due to gynecological disease at Yonsei University Colloge of Medicine were analyzed. We measured c-erbB-2 oncoprotein with an enzyme-linked immunosorbent assay(ELISA) which was a sandwich type. Patients with invasive ovarian cancer were found to have significantly higher median c-erbB-2 oncoprotein expression than patients with either benign ovarian cyst(P<0.05) or control group(P<0.05), respectively. However there was no significant difference in c-erbB-2 oncoprotein status between benign cyst and control group. verexpression of c-erbB-2 oncoprotein was found in 7 of 32(21.9%) epithelial ovarian cancer. In invasive epithelial cancer, no significant difference in c-erbB-2 oncoprotein levels was noted when stratified according to age, menopausal status, histological cell type, tumor size or surgical stage. Our results were consistent with the concept that c-erbB-2 oncoprotein may play an important role in malignant and tumorigenesis in epithelial ovarian cancer.
Adenocarcinoma ; Breast ; Carcinogenesis ; Cervix Uteri ; Female ; Genes, vif ; Humans ; Hysterectomy ; Oncogenes ; Ovarian Neoplasms ; Ovary ; Prognosis ; Protein-Tyrosine Kinases ; Receptor, Epidermal Growth Factor ; Salivary Glands

Based on the facts that expression of insulin-like growth factors(IGFs), their receptors, and insulin-like growth factor binding proteins(IGFBPs) have been found in many different types of malignancies including human ovarian cancer and their potent mitogenic effects in vitro, a role for IGFs mediated autocrine loop in oncogenesis and growth regulation of human malignancies was suggested. Since ascites support the biological environment for advanced ovarian cancer, it seemed to be resonable to measure the level of growth factors or cytokines in ascites for understanding precise mechanism of those factors in tumor biology. To investigate their roles and to evaluate prognostic significance in ovarian cancer, the IGFs/IGFBPs system were studied in the ascites, not in sera or cystic fluids, from 22 patients with ovarian cancer, who underwent surgical staging and subsequent cis-platinum based systemic chemotherapyery at the Department of Obstetrics and Gnecology, Hanyang University Hospital from Jan. 1989 through Dec. 1994. Ascites from 7 patients with benign disease were used as the control. IGF-I, II, IGFBP-1, and 3 were measured by immunoradiometric assay. The IGF-I level was significantly higher in ascites with ovarian cancer compared with those of benign disease(63.3-/+11.1 vs 17.9-/+6.2ng/ml, p=0.0098), but the level of IGF-II was not significantly different(70.5-/+13.9 vs 70.8-/+31.5 ng/ml, p=0.2827). IGFBP-1 levels were tend to be lower in ascites of patients with ovarian cancer than that of control(25.2-/+9.5 vs 58.6-/+28.2ng/ml, p=0.0637). However, IGFBP-3 levels had no statistically significant difference between two groups(779.7-/+110.6 vs 674.7-/+175.1ng/ml, p=0.8328). Although growth hormone levels were significantly higher in ascites with metastatic ovarian cancer than those of primary epithelial ovarian cancer, the levels of IGF-I, II, IGFBP-1 and 3 in ascites were not significantly different between two groups. IGF-I levels were correlated with the levels of IGFBP-3 in ascites with ovarian cancer(Y=8.83X-2.0, r=0.745, p=0.0000). High level of IGF-I in ascites of patients with ovarian cancer in this study was suggested that IGF-I had an important role on growth regulation of ovarian cancer. As majority of ascites were obtained from advanced and poorly differentiated ovarian cancer patients, IGF-I in ascites seemed to be related with intraperitoneal metastasis. Further large number of study including data from sera or cystic fluid will be needed to elucidate the role of the IGFs and IGFBPs in ascites of patients with ovarian cancer.
Ascites* ; Biology ; Carcinogenesis ; Cisplatin ; Cytokines ; Growth Hormone ; Humans ; Immunoradiometric Assay ; Insulin-Like Growth Factor Binding Protein 1 ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor Binding Proteins* ; Insulin-Like Growth Factor I ; Insulin-Like Growth Factor II ; Intercellular Signaling Peptides and Proteins ; Neoplasm Metastasis ; Obstetrics ; Ovarian Neoplasms* ; Somatomedins*

OBJECTIVE: To evaluate the status of cone margins and severity of cervical neoplasia as predictors of residual lesions in the remaining cervices, and provide guideline for further treatment or close follow-up. METHOD: We performed a 3-year retrospective study and reviewed 95 patients who had undergone cervical conization followed by subsequent hysterectomy. RESULT: The prevalence rates of positive cone margins were 33, 50, 44, 71 and 88% respectively in patients with cervical intraepithelial neoplasia(CIN)II, CIN III, cervical cancer stage Ia1, Ia2 and Ib1. The prevalence rates of positive residual lesions in postcone hy-sterectomy specimens were 0, 31, 19, 29 and 59% respectively in patient with CIN II, CIN III, cervical cancer Ia1, Ia2 and Ib1. Residual lesions were significantly more frequently found in patients with positive cone margins(51%) than in those with negative margins(4.8%). Positive predictive values of margin status for the presence of residual lesions were 0, 56, 36, 40 and 67% respectively. Negative predictive values of margin status for the absence of residual lesions were 100, 94, 94, 100 and 100% respectively. CONCLUSIONS: (1) The prevalence of positive cone margin and residual lesion increased with more severe cervical neoplasia. (2) Positive cone margins had significantly higher risks of residual lesion than negative cone margins. (3) Positive cone margin does not invariably indicate the presence of residual lesion. (4) Negative cone margin does not ensure the absence of residual lesion. Subsequent hysterectomy may be reserved for the patient with CIN III or cervix cancer having positive cone margin or invasive lesion, or the patient who is not reliable for continuous follow-up.
Conization* ; Follow-Up Studies ; Humans ; Hysterectomy ; Prevalence ; Retrospective Studies ; Uterine Cervical Neoplasms

OBJECTIVE: The purpose of this study is to evaluate the histologic correlations and the clinical significance among patients with atypical squamous cells of undetermined significance (ASCUS), atypical glandular cells of undetermined significance(AGUS) and benign endometrial cells identified on cervical Pap smear screening. MATERIALS & METHODS: The computerized files of the Department of Pathology at Samsung Cheil Hospital were searched from 1991 to 1997 to evaluate the annual statistics of cytologic diagnoses including normal/benign, ASCUS, AGUS, low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion(HSIL) and cancer classified by the Bethesda System(TBS). Cytohistologic correlations on follow-up were separately analysed in ASCUS(190 cases), AGUS(268 cases) and benign endometrial cells(169 cases), respectively. Additionally, post-menopausal squamous atypia(83 cases) were also included in this study. TBS terminology was used in both cytologic and histologic diagnoses. RESULTS: During 7-year period (1991-1997), 447,049 cervicovaginal smears were evaluated. The median rate of abnormal cytology was 4.4%, with 2.1% of ASCUS, 2.06% of squamous intraepithelial lesion(SIL), and 0.08% of AGUS. The median ratio of ASCUS versus SIL was 1.24. Specimen adequacy was evaluated on 47,525 cases, of which categories of "satisfactory for evaluation but limited by" and "unsatisfactory for evaluation" were 28.3% and 0.03%, res-pectively. Follow-up of 190 patients with ASCUS cytology showed 30%(57 cases) with SIL on biopsy; 18%(35cases) with LSIL, 11%(21cases) with HSIL, and 1%(1case) with microinvasive squamous cell carcinoma. On histologic examination, 77%(37/48cases) with ASCUS favoring SIL revealed SIL in contrast to 14%(20/142cases) with ASCUS favoring reactive change, which is statistically significant.(Chi-Square test, P<0.0001). Of 83 cases of post-menopausal squamous atypia(PSA), smears with LSIL showed 34.9%(15/43cases) with LSIL on biopsy. 268 patients with AGUS smears had 25%(67cases) with clinically significant cervical or endometrial lesions on histologic examinations. Among 17.9%(48cases) with cervical lesions, squamous abnormalities were 10.5%(28cases); including 1.5%(4cases) with LSIL and 9.0%(24cases) with HSIL. Glandular lesions in cervix were 7.5%(20cases); 3.0%(8cases) of glandular atypia or dysplasia, 1.9%(5cases of adenocarcinoma in situ, 1.1%(3cases) of microinvasive adenocarcinoma and 1.5%(4cases) of adenocarcinoma. Of 7.1%(19cases) of endometrial lesions, 2.2%(6cases) was endometrial hy-perplasia, 4.1%(11cases) endometrial carcinoma, 0.4%(1case) MMMT and 0.4%(1case) metastatic adenocarcinoma from stomach were verified. The pathologies of 169 cases with benign endometrial cells shed in cervicovaginal smears were confirmed to be endometrial polyp(8.3%), endometrial hyperplasia(4.1%) and endometrial carcinoma(5.9%). CONCLUSION: The results of this study indicates that clinicians should communicate with pathologists for proper management of abnormal cytology. Further evaluation and decision of management should be made based on input from pathologists as well as on clinical setting and professional guidelines.
Adenocarcinoma ; Biopsy ; Carcinoma, Squamous Cell ; Cervix Uteri ; Diagnosis ; Endometrial Neoplasms ; Female ; Follow-Up Studies ; Humans ; Mass Screening ; Pathology ; Stomach

To evaluate the efficacy and diagnostic and prognostic significance of two tumor markers (SCCA, CA 125) in patient with squamous cell carcinoma of uterine cervix, the authors studied 215 patients with squamous cell carcinoma in situ and invasive carcinoma from September 1993 to November 1996. Both tumor markers were measured coincidently in 215 patients preopera-tively and in 70 cases of benign gynecologic disease for control group. Serum SCCA level of 2.5 ng/ml and CA 125 level of 35.0 U/ml were determined as cut-off levels. The results were as follows: 1. The pretreatment positive rate of SCCA in patient group were 35.8 %(77/215) and 5.7 %(4/70) in control group. 2. The mean values and positive rates of SCCA according to clinical stage were 1.44+/-3.59 ng/ml(8.7 %) for stage 0, 3.81+/-10.22 ng/ml(23 %) for stage I, 8.54+/-15.23 ng/ml(51.3 %) for stage II, 35.54+/-38.34 ng/ml(70.0 %) for stage III, 22.49+/-36.06 ng/ml(75.0 %) for stage IV, 40.33+/-58.66 ng/ml(66.7 %) for recurrent cancer, respectively. The mean SCCA value and positive rate were significantly increased stepwise by clinical stage from stage I to stage III (P<0.05). 3. The pretreatment positive rate of CA 125 in patient group were 21.9 %(47/215) and 17.1 %(12/70) in contrl group. 4. In pre-invasive and invasive groups, the mean value and positive rate of SCCA were 1.44+/-3.59 ng/ml(8.7 %), 9.05+/-25.26 ng/ml(43.2 %), respectively, and it was statistically significant between two groups (P<0.05). The mean values and positive rate of CA 125 were 24.36+/-16.14 U/ml(10.9 %), 35.15+/-59.52 U/ml(24.9 %), respectively, it was not statistically significant (P>0.05). 5. The result of preoperative serum levels of SCCA can be characterized by 35.8 % sensitivity, 94.3 % specificity, 95.1 % positive predictive value, 32.4 % negative predictive value, 49.5 % diagnostic efficiency, and with 21.9 %, 82.8 %, 79.7 %, 25.7 %, 36.8 % respectively for CA 125. Between these two tumor markers, the result of SCCA was more valuable than the other in sensitivity, positive predictive value, negative predictive value and diagnostic efficiency. The results indicate that measurement of SCCA and/or CA 125, have little efficacy in the early detection of squamous cell carcinoma considering it's low rate of positivity in preinvasive and early stage of invasive squamous cell carcinoma. However, in patients with advanced stage invasive carcinoma, measurement of serum SCCA is useful in prediction of prognosis and in early detection of recurrence, and concomitant measurements of SCCA and CA 125 may be more useful in determining prognosis, therapeutic response, and early detection of recurrence than measurement of SCCA alone.
Carcinoma, Squamous Cell* ; Cervix Uteri* ; Female ; Genital Diseases, Female ; Humans ; Prognosis ; Recurrence ; Sensitivity and Specificity ; Biomarkers, Tumor*

Small cell carcinoma of the ovary has been identified as a specific histopathologic entity. The first II cases were reported by Dickersin et a1, 1982, Since then only 80 cases were reported in literature. This rare and highly aggresive melignancy primarily affeets ehildren and young women(10-40) and grows rapidly, with hypercalcemia occuring frequently. Abscence of effective treatment results in early mortality. Recently we have experienced one case of primary sma11 cell carcinoma of the ovary, which is presented with a brief review of the literature.
Carcinoma, Small Cell* ; Female ; Hypercalcemia ; Mortality ; Ovary*