CD44v6 as a prognostic factor in cervical carcinoma FIGO stage IB.

The aim of our study was to clarify whether CD44v6 evaluation can serve as a universally applicable prognostic factor in patients with FIGO stage IB cervical carcinoma. A retrospective study was performed on 178 FIGO stage IB (142 IB N0, 36 IB N1) radically operated cervical carcinoma patients. The expression of CD44v6 was investigated by immunohistochemistry (IHC). The prognostic significance of established prognostic factors and CD44v6 expression was analyzed by univariate and multivariate analyses. To test the reproducibility and to account for interobserver variability, all specimens were evaluated independently at two institutions. Two different IHC scoring systems, several cut-off levels for CD44v6 positivity and several statistical methods for IHC results evaluation were used. In a univariate analysis, the most significant prognostic factor for overall survival (OS) was lymph node status (p<0.001) followed by tumor volume, LVSI, GOG score (p<0.01) and a deep stromal invasion (p = 0.06). We found a strong correlation between CD44v6 expression and squamous cell carcinoma (SCC) (SCC vs. adenocarcinoma - p<0.001) and between CD44v6 expression and deep stromal invasion, LVSI and GOG score (p<0.05). The CD44v6 expression was not a statistically significant prognostic factor for OS in a univariate analysis (p=0.39 Vienna; p=0.54 Freiburg). In a multivariate analysis, the most significant prognostic factor for OS was lymph node status (p =0.002), followed by tumor diameter and LVSI (p<0.05). CD44v6 expression was not a statistically significant prognostic factor for OS or disease-free interval (DFI) independent of the scoring method used. In conclusion, we demonstrated that CD44v6 expression is associated with LVSI, deep stromal invasion and SCC, but has no prognostic influence on OS and DFI in a population of 178 women with FIGO stage IB cervical carcinoma.

Cathepsin D in ovarian cancer: prognostic value and correlation with p53 expression and microvessel density.

OBJECTIVE: Overexpression of ubiquitous lysosomal aspartyl protease cathepsin D (CD) is involved in the progression of cancer. This study investigates the prognostic value and the association of cathepsin D expression with clinicopathological parameters, p53 expression, and angiogenesis in ovarian cancer. METHODS: Cathepsin D was determined immunohistochemically in 43 ovarian tumors of low malignant potential (LMP) and 80 invasive tumors FIGO stage I-IV. Results were correlated with clinicopathological characteristics, p53, and microvessel density (MVD). Survival analysis of cathepsin D expression and MVD was performed in invasive tumors. RESULTS: Epithelial tumor cathepsin D expression was more common in LMP tumors (65.1%) compared to invasive tumors (43.7%; P = 0.02). In LMP tumors, stromal cathepsin D was associated with mucinous tumors (P = 0.01), whereas in invasive tumors, epithelial cathepsin D expression was associated with clear cell tumors (P = 0.003). Invasive tumor cathepsin D had a negative relation to p53 expression. In LMP tumors, stromal cathepsin D correlated with microvessel density (P = 0.03). Stromal cathepsin D expression was an independent prognostic factor for disease-free survival (DFS) in patients with invasive cancer (P = 0.03, Cox regression), while cathepsin D expression missed to be of prognostic value for overall survival (OS) in invasive ovarian cancer. MVD had no influence on survival in invasive ovarian cancer (P > 0.05). CONCLUSION: Our study demonstrates a prognostic value of cathepsin D expression in invasive ovarian cancer, while cathepsin D expression in LMP tumors seems to be linked to angiogenesis. The relation among cathepsin D, p53 expression, and angiogenesis demonstrates biological differences between invasive ovarian cancer and LMP tumors.

Immunohistochemical expression of laminin-5 in cervical intraepithelial neoplasia.

OBJECTIVES: Laminin-5 is an attachment protein for epithelial cells. Several studies of a variety of cancers have reported increased expression of laminin-5 in carcinoma in situ and invasive cancer. This study was designed to investigate the correlation between the grade of cervical intraepithelial neoplasia and the immunohistochemical expression of laminin-5 in the cytoplasm and in the basement membrane underlining dysplastic squamous cells. METHODS: We used immunohistochemical methods to stain paraffin-embedded sections of cervical cone biopsies with a monoclonal antibody specifically targeting the 2-chain of human laminin-5 protein. The study sample included 175 slides: 7 normal cervical epithelium, 36 lesions of mild dysplasia, 50 lesions of moderate dysplasia, 81 lesions of severe dysplasia, and 1 invasive squamous cell carcinoma. RESULTS: We found a statistically significant correlation between the grade of cervical intraepithelial neoplasia and laminin-5 immunoreactivity in the cytoplasm (P < 0.01) and in the basement membrane (P = 0.03) by use of the Wilcoxon rank-sum test. CONCLUSIONS: According to previously published reports we confirmed with a higher number of cases a correlation of laminin-5 expression in the cytoplasm and/or basement membrane and grade of dysplastic lesion in the cervical epithelium. This study warrants further investigations with special interest to follow-up to investigate whether laminin-5 is a marker to predict the risk of progression of cervical intraepithelial neoplasia lesions.

Adenovirus-mediated thymidine kinase gene therapy for recurrent ovarian cancer: expression of coxsackie-adenovirus receptor and integrins alphavbeta3 and alphavbeta5.

OBJECTIVE: Ten patients with recurrent ovarian cancer received a combined treatment of optimal tumor debulking, adenovirus-mediated herpes simplex virus thymidine kinase gene therapy (GT), and systemic application of acyclovir or valacyclovir and topotecan. Biopsies were taken at the time of secondary debulking about 1 month after the application of GT and chemotherapy and were analyzed for expression of coxsackie-adenovirus receptor (CAR) and integrins alphavbeta3 and alphavbeta5 with respect to treatment response. METHODS: Treatment modalities and study design have been described recently. Immunohistochemistry was used to visualize expression of CAR and integrins alphavbeta3 and alphavbeta5 in tumor samples taken before and after application of GT. RESULTS: Before GT six of ten patients presented with CAR-positive and four with CAR-negative tumors. After GT all tumors showed CAR expression. Integrin alphavbeta3 was found in all tumors before and after GT. Expression of integrin alphavbeta5 was seen in eight of ten tumor samples before GT and in all samples after GT. CONCLUSION: Despite the importance of CAR and integrin expression for successful adenovirus internalization, other cell surface receptors might be involved in this process. It is too early to decide whether expressions of CAR and integrin alphavbeta3/alphavbeta5 on tumor cells are appropriate additional inclusion criteria for the enrollment of patients in GT trials. Further research is necessary to evaluate the effect of GT plus chemotherapy on CAR and integrin expression.

Histologic and immunohistochemical analysis of tissue response to adenovirus-mediated herpes simplex thymidine kinase gene therapy of ovarian cancer.

Herpes simplex virus (HSV) thymidine kinase (tk) gene incorporated into adenovirus was delivered intraperitoneally (ip) followed by an antiherpetic prodrug and topotecan in patients with recurrent epithelial ovarian cancer. Tissue response was evaluated. Ten patients underwent secondary debulking with subsequent delivery of ADV-HSV-tk therapy. Two patients each were treated at dose level 1 (2 x 10(10) vector particles = VP), 2 (2 x 10(11) VP), and 3 (2 x 10(12) VP); four patients were treated at dose level 4 (2 x 10(13) VP). Five patients underwent second-look surgery about one month after gene therapy (GT). Treatment response, presence of vector DNA, protein expression of steroid hormone receptors, p53, c-erbB2 and Ki67 protein were analyzed. At second-look, two out of five patients were tumor-free and none of their peritoneal biopsies showed vector DNA. After GT, the vital tumor mass was smaller, desmoplastic reaction had increased, and tumors were less differentiated with an increase of Ki67 expression. There was no change in expression of hormone receptors, p53, or c-erbB2. ADV-HSV-tk GT appears to eliminate cells with higher differentiation first and might induce fibrosis. Dedifferentiation might render residual cells more sensitive to chemotherapy secondary to their subsequent higher mitotic activity.

Prognostic value of beta1-integrin (=CD29) in serous adenocarcinomas of the ovary.

BACKGROUND: Integrins are heterodimeric transmembranous proteins, comprised of two transmembrane subunits, called alpha and beta. They bind to various structures of the extra cellular matrix (ECM) and are responsible for cell-cell interactions. The aim of the current study was to evaluate the prognostic value of beta1-integrin in patients suffering from malignant serous surface epithelial-stromal tumors of the ovary. MATERIALS AND METHODS: With immunohistochemical methods we investigated 76 formalin-fixed, paraffin-embedded tissue samples. FIGO stages I, II, III and IV were present in 18, 10, 41 and 7 cases, respectively. RESULTS: 12 sections (15.8%) stained positive for beta1-integrin (=CD29), 64 sections (84.2%) showed no expression of beta1-integrin. The product limit method by Kaplan and Meier showed no statistical significance of beta1-integrin expression on overall survival, (p = 0.1005, log-rank test). Also the univariate Cox regression analysis showed no statistical significance of beta1-integrin expression on overall survival (p=0.1066), whereas in the multivariate analysis, adjusted for grading, FIGO stage and residual tumor, the expression of beta1-integrin turned out to be significantly correlated with reduced overall survival (p=0.0208). CONCLUSION: Our results using multivariate Cox regression analysis indicated a shorter overall survival for patients with positive staining for beta1-integrin in malignant serous surface epithelial-stromal tumors of the ovary. This pilot study warrants further investigation of the role of beta1-integrin in ovarian cancer.

Immunohistochemical detection of lymph node metastases in node-negative breast cancer patients.

BACKGROUND: Axillary lymph node metastases in breast cancer patients are one of the most important prognostic factors. Many previous studies have shown that in the detection of occult micrometastases immunohistochemical methods are superior when compared to routine hematoxylin-eosin staining. The aim of the study was to document the rate of missed occult micrometastases on routine hematoxylin-eosin staining in our department, in a retrospective study. PATIENTS AND METHODS: One hundred and one tumors of patients with breast cancer were included in this study. Immunohistochemical staining was performed using Pan-Cytokeratin AE1/AE3 antibody. The number of nodes examined was 1301 (mean per patient: 12.9; range: one to 26). RESULTS: Of the 101 tumors studied, eleven had occult lymph node metastases detected by immunohistochemical methods. After repeated review by two independent pathologists, in two out of eleven patients lymph node metastases were confirmed even on hematoxylin-eosin staining. In nine out of eleven patients hematoxylin-eosin staining was not sufficient to detect occult micrometastases. CONCLUSION: Immunohistochemical methods enhance the detection rate of occult micrometastases in axillary lymph nodes of breast cancer patients and are recommended for routine diagnostic use in patients who have been diagnosed node-negative on routine hematoxylin-eosin staining.

Laparoscopic port-site recurrence following surgery for a stage IB squamous cell carcinoma of the cervix with negative lymph nodes.

BACKGROUND: Port-site metastases are commonly reported after laparoscopic surgery for ovarian cancer, but have also been reported in patients with cervical or endometrial cancer with positive lymph nodes. Recently, a case of port-site recurrence after laparoscopic surgery for a patient with node-negative early-stage adenocarcinoma of the cervix was reported. We report the first case of port-site metastasis in a patient with stage IB squamous cell carcinoma of the cervix with negative lymph nodes. CASE: A 31-year-old woman had a laparoscopy for pelvic pain. Under anesthesia, she was noted to have a grossly abnormal-looking cervix and a biopsy revealed squamous cell carcinoma. She was referred to a gynecological oncologist and underwent radical hysterectomy and pelvic lymph node dissection through a transverse lower abdominal incision 6 weeks later. Nineteen months postoperatively, she presented with a soft tissue mass in a suprapubic laparoscopic trocar site. CONCLUSION: It is postulated that cells dislodged at the time of cervical manipulation and biopsy may have passed through the fallopian tubes and implanted in the laparoscopic port site due to the "chimney effect" caused by the pneumoperitoneum.

Immunohistochemical detection of estrogen and progesterone receptor in human cornea.

OBJECTIVE: For treatment of postmenopausal keratoconjunctivitis sicca hormone therapy is favored by some clinicians. The likely morphological basis assessing the hormone receptor status in the human cornea has not been performed. Immunohistochemical staining methods provide the opportunity to evaluate the hormone receptor content within the histologic compartments of the cornea. The aim of our study was to assess and localize immunohistochemical hormone receptor staining in the human cornea. METHODS: Formalin-fixed and paraffin-embedded specimens of three pre- and three postmenopausal women were assessed for localization of estrogen receptor (ER) and progesterone receptor (PR) expression with established immunohistochemical hormone receptor staining methods. RESULTS: No nuclear staining reaction was found in the epi- and endothelial layers of the corneas. The stroma of the corneas showed no immunohistochemical staining reaction in all cases. We found cytoplasmatic PR staining of the endothelial layer in two cases. CONCLUSIONS: We found no morphological basis in the human cornea for the use of topical steroid hormone treatment in postmenopausal keratoconjunctivitis sicca. Hormone receptor expression in the conjunctiva or in the lacrimal gland may have an impact in some patients showing relief of symptoms in postmenopausal dry eye syndrome.

[Sacrococcygeal teratoma in obstetrics]. / Das Steissteratom in der Geburtshilfe.

MATERIALS/METHODS: 5 fetuses with prenatally diagnosed sacrococcygeal teratoma at the Department of Prenatal Diagnosis and Therapy during a 30-month period. Modified splint technique according to Duzin, following a Pfannenstiel's incision in 4 cases. RESULTS: 4 infants with uninjured tumor could be transferred to pediatric surgery for treatment. CONCLUSIONS: The modified splint technique according to Duzin can be applied particularly in the case of a big tumor.

Comparative evaluation of seven cell collection devices for cervical smears.

OBJECTIVE: To compare the most commonly used cervical sampling devices. STUDY DESIGN: We examined seven cytology sampling devices (Cytobrush, Cervex brush, Szalay spatula, Papex spatula, WrGKK spatula [main social security agency in Vienna], cotton swab and loop). Eight hundred smears were assessed for even distribution of cells, percentage of slide surface covered with cells, and presence and number of endocervical cells. RESULTS: Even distribution of cells was best with the WrGKK spatula. Percentage of slide surface covered with evaluable cells was best with the Cytobrush. Highest ranking for the presence of endocervical cells was found for the Cytobrush. Cotton swabs and loop showed inferior results in all categories. CONCLUSION: The use of cervical cell sampling devices showing the best cytologic results improves the interpretation and validity of cervical smears. Our results suggest that cotton swabs and loops should not be used for cervical cell sampling.

Serum p53 autoantibodies in patients with minimal lesions of ductal carcinoma in situ of the breast.

Five of 43 patients (11.6%) with ductal carcinoma in situ of the breast presented with p53 autoantibodies at diagnosis. Three seropositive patients demonstrated tumour sizes of < or = 5 mm. There was no association of p53 autoantibody status with age, clinical presentation, histological subtype, tumour size, grading, p53 immunohistochemistry or hormone receptor status.

Fluorescence in situ hybridization in cervical smears: detection of numerical aberrations of chromosomes 7, 3, and X and relationship to HPV infection.

BACKGROUND: Human papillomavirus (HPV) is known to play a pivotal role in cervical carcinogenesis. Chromosomal aberrations are known to be related to different biological behaviors of malignant lesions. We analyzed whether numerical chromosomal aberrations, related to more aggressive tumor types, are found not only in high-grade squamous intraepithelial lesions (HSIL) but also in low-grade SIL (LSIL) of the cervix and evaluated their relationship to HPV infection. METHODS: Eighty women (19 to 74 years of age) were included in this study and grouped according to the Bethesda System: within normal limits (WNL), LSIL, and HSIL. By FISH, chromosomes 7 and X, and in part chromosome 3, were analyzed for numerical aberrations. Using the hybrid capture system HPV detection was performed. RESULTS: All 20 patients with cervical smear WNL had regular diploid chromosomal pattern and were negative for HPV. Thirteen of the 29 (41.2%) patients with LSIL showed trisomy 7, in association with trisomy X in 4 cases (12.9%). Single trisomy X was detected in 4 cases (12.9%). In 3 of 15 (20%) cases analyzed for chromosome 3 trisomy was observed. Trisomy 3 was associated with trisomy 7 and X or with trisomy 7 alone. The hybrid capture test was performed in 16 patients of this group. Two patients were positive for HPV probe A, 9 for probe B, and 2 for A and B, and 3 patients were negative. Twenty-three of the 29 patients (79.3%) with HSIL showed trisomy 7. Twelve of the 29 patients (41.3%) had an additional trisomy X. Single trisomy X was seen in only 2 cases (6. 9%). Twenty-two patients with HSIL were tested also for chromosome 3. Nine of the 22 patients (40.9%) showed trisomy 3, associated with trisomy 7 or with trisomy 7 and X. In 25 of the 29 patients HPV detection by the hybrid capture system was performed. HPV probe B was positive in 15 cases (60%). One patient was positive for both probes, A and B. Nine (36%) of the patients with HSIL were negative for both HPV probes. No positivity was observed for HPV probe A alone. CONCLUSION: Our data confirm the pivotal role of HPV in cervical carcinogenesis as it seems to cause changes in the chromosomal pattern of premalignant lesions. Additionally, trisomy 7 may be considered an early event in cervical carcinogenesis, persisting and increasing with progression of the lesion. The roles of trisomy 3 and X need further evaluation.

Modified true-color computer-assisted image analysis versus subjective scoring of estrogen receptor expression in breast cancer: a comparison.

BACKGROUND: Hormone receptor expression can be quantified by computerized image analysis in immunohistochemically stained specimens. When comparing semiquantitative scoring with computerized image analysis a review of the literature shows contradictory findings concerning the correlation of these two methods. Recent technical approaches have been developed with true-color computer-assisted image analysis facilitating new measurement designs. We performed a study with a new approach using the principle of semiquantitative assessment of hormone receptor content and measuring two different binary images (immunohistochemically stained nuclear area and total nuclear area). MATERIAL AND METHODS: Eighty formalin-fixed, paraffin-embedded and immunohistochemically stained breast cancer specimens were assessed for estrogen receptor expression by true color computer-assisted image analysis and by conventional light microscopy scoring according to Remmele (immunoreactive score (IRS) = staining intensity (SI) x percentage of positive cells (PP)). The results of both methods were correlated. RESULTS: Mean optical density (MOD) and subjective scoring of SI as well as stained nuclear area vs. total nuclear area and subjective scoring of stained cells (PP) showed a high correlation (Spearman correlation coefficient: 0.95, p-value: 0.0001 and 0.64, p-value: 0.0001, respectively). CONCLUSION: On the basis of this new technical approach our results confirm the correlation of semiquantitative hormone receptor scoring and quantitative computer-assisted image analysis. We believe that by automating electronic analysis in the near future we will be able to establish reliable observer-independent evaluation of immunohistochemical variables ensuing comparability in multi-center trials and cost efficiency.

Evidence of androgen receptor expression in lichen sclerosus: an immunohistochemical study.

OBJECTIVE: While topical androgen administration is widely used in the treatment of lichen sclerosus of the vulva, localization and level of expression of androgen receptor (AR) have not been described previously. METHODS: Thirty-nine paraffin-embedded punch biopsies of patients with lichen sclerosus of the vulva were examined. Androgen receptor, estrogen receptor (ER), and progesterone receptor (PR) expression in lichen sclerosus and in normal vulvar skin were investigated by immunohistochemistry. RESULTS: Five tissue specimens (12.8%) of lichen sclerosus showed nuclear staining with anti-AR in the parabasal cell layers of the epidermis. Median age of patients with positive nuclear staining for AR versus women without AR expression was 71 (range, 63-78) and 66.5 (range, 38-91) years, respectively. Estrogen receptor expression was present in only one patient. Nuclear staining reaction for PR expression was absent in all cases. Four of the five AR-positive women reported no complaints and therefore received no topical testosterone therapy. CONCLUSION: Our results suggest a lack of complaints in AR-positive lichen sclerosus patients. Our findings could justify a larger study comparing symptoms of patients with and without AR expression.

p53 protein overexpression: a strong prognostic factor in uterine papillary serous carcinoma.

Uterine papillary serous carcinoma (UPSC) is an uncommon but aggressive type of endometrial cancer associated with rapid progression of disease and poor prognosis. We investigated 23 cases of UPSC. p53 expression was studied in archival paraffin-embedded tissue by immunohistochemistry. Eleven tumors (47.8%) showed p53 overexpression whereas 12 tumors (52.2%) were p53 negative. One of 8 stage I/II (12.5%) and 10/15 stage III/IV (66.6%) tumors revealed p53 staining (P = 0.027). The median overall survival was 43.3 months. Patients with advanced-stage (III, IV) disease had a 5-year overall survival probability (5-year OS%) of 24% compared to 100% in those in stages I and II (log-rank, P = 0.018). Myometrial invasion, lymphatic space invasion, or lymph node involvement did not correlate with the 5-year OS of these patients. Patients whose tumors overexpressed p53 had a significantly shorter survival than those whose tumors did not (P = 0.033). This study confirms the influence of p53 overexpression on survival in UPSC patients.

Prognostic value of cathepsin D expression and association with histomorphological subtypes in breast cancer.

This study investigated the prognostic value of immunohistochemically detected cathepsin D expression in 103 invasive ductal carcinomas of the breast at stages pT1 and 2. We also assessed the association between cathepsin D expression and histomorphological tumour subtypes (invasive ductal carcinoma with extensive intraductal component, multifocal tumour). Cathepsin D expression was examined at two cut-off levels (positive and highly positive) and separately identified within the epithelial and stromal component of all tumours. Positive and highly positive epithelial expression was detected in 32 (31.1%) and 20 (19.4%) patients respectively. Stromal expression was found in 35 (34%) and 19 (18.4%) cases respectively. Epithelial cathepsin D expression was associated with stage and nuclear grade, but not with lymph node or oestrogen receptor status. Positive and highly positive epithelial cathepsin D expression showed significant prognostic value for overall survival (P = 0.003 and 0.01) and recurrence-free interval (P = 0.04 and 0.02). Cathepsin D expression in stromal cells was not associated with either several established prognostic factors or survival. Multivariate analysis revealed that cathepsin D expression failed to be an independent predictor of patients' outcome. Cathepsin D expression shows no significant association with histomorphological subtypes of breast cancer. Our study supports the prognostic impact of immunohistochemically detected cathepsin D expression in the epithelial component of breast cancer.

Evaluation of needle size for breast biopsy: comparison of 14-, 16-, and 18-gauge biopsy needles.

OBJECTIVE: The purpose of our study was to compare the quantity and quality of tissue harvested from breast biopsy when using 14-, 16-, and 18-gauge "long-throw" needles. SUBJECTS AND METHODS: We performed a prospective randomized study in 64 patients with 66 breast lesions. Under stereotactic guidance, passes were made in random order with each of the three biopsy needles in each lesion. Samples were measured for tissue area and scored for their quality. All lesions, including benign and malignant lesions and lesions with and without microcalcifications, were analyzed. Findings of the biopsy samples were compared with the final diagnoses made at surgical excision. RESULTS: In all 66 lesions, 14-gauge biopsy needles obtained significantly larger specimens (14-gauge, 13.14 mm2; 16-gauge, 9.6 mm2; 18-gauge, 6.41 mm2; p < .05) and scored significantly better (14-gauge, 8.37; 16-gauge, 7.56; 18-gauge, 7.14; p < .016) than either of the smaller needles. The results for malignant and benign lesions and for lesions with and without microcalcifications were similar but not equal to the overall results. However, benign lesions and areas with microcalcifications seem to be more problematic for both smaller needles than for 14-gauge needles. CONCLUSION: Our results indicate that the quantity and quality of breast biopsy specimens depend on the needle size. Of the three needle sizes tested, only 14-gauge long-throw biopsy needles can be recommended for breast biopsy.

Absence of p53 protein overexpression in precancerous lesions of the vulva.

BACKGROUND: Recently the authors reported the prognostic value of p53 protein overexpression in invasive squamous cell carcinoma of the vulva. The aim of this study was to evaluate the status of p53 overexpression and human papillomavirus (HPV) infection in patients with precancerous lesions of the vulva. METHODS: Biopsy specimens of 28 women (mean age, 44.2 years; range, 19-71 years) with warty and/or basaloid type vulvar intraepithelial neoplasia (VIN) of Grade 1 to 3 were examined retrospectively for p53 protein overexpression by immunohistochemistry. The presence of the HPV genome was assessed using a nested polymerase chain reaction (PCR) method with consensus primers directed against the L1 coding region. RESULTS: Neither the preoperative punch biopsy specimen nor the subsequent surgical specimen contained immunohistochemically detectable levels of p53 in this study of a group of younger women with preinvasive vulvar lesions. These results are in contrast to those obtained previously in older women with keratinizing squamous cell carcinoma demonstrating p53 protein overexpression in approximately 50% of patients. HPV DNA was detected in the vast majority of VIN cases (92.8%) using a highly sensitive nested PCR method. The current data indicate that p53 protein is not overexpressed in basaloid/warty VIN when evaluated by immunohistochemistry. In addition, this study confirms previous reports demonstrating the presence of HPV DNA in the majority of these lesions. CONCLUSIONS: These data suggest that p53 protein overexpression is not an early event in the pathogenesis of basaloid/warty type vulvar dysplasia and that HPV infection may contribute to the development of VIN.

Numerical chromosomal aberrations in borderline, benign, and malignant epithelial tumors of the ovary: correlation with p53 protein overexpression and Ki-67.

OBJECTIVE: Ovarian tumors of low malignant potential (borderline tumors) have a 5-year survival rate of 69-98%, illustrating that while the prognosis is better than in the typical epithelial carcinoma, a significant number of women still succumb to this disease. The aim of our study was to elucidate the role of numerical chromosomal aberrations in borderline tumors of the ovary in comparison with benign and malignant epithelial tumors in an effort to develop parameters to differentiate prospectively borderline lesions from benign and invasive tumors. METHODS: Cytologic imprints of surgical specimens of 46 ovarian tumors of low-malignant potential, 17 invasive epithelial carcinomas of the ovary, and 18 benign epithelial tumors of the ovary were examined for numerical chromosomal aberrations (trisomy 7, trisomy 12, and trisomy 17) by fluorescence in situ hybridization (FISH). RESULTS: In benign tumors no evidence of trisomy 7 and 17 was present. Trisomy 12 was detected in six cases (33.3%). We did not find p53 protein overexpression in any case. Ki-67 stained positive in three cases (16.7%). In borderline tumors trisomy 12 was detected in 33 patients (71.7%). Numerical aberrations of chromosome 17 were absent in all cases. Fourteen patients (30.4%) showed trisomy 7. No immunohistochemical staining reaction for p53 protein was found. Staining of the proliferation marker Ki-67 was observed in two cases (4.3%). In malignant epithelial tumors of the ovary, trisomy 7, trisomy 12, and trisomy 17 were detected in 14 (82.3%), 11 (64.7%), and 5 (29.4%) cases, respectively. Four tumors (23.5%) showed immunohistochemically detected p53 protein overexpression. Thirteen tumors (76.5%) stained for Ki-67. CONCLUSION: Our results indicate that trisomy 7 argues against benign disease. Trisomy 17 was specific for invasive disease, while trisomy 12 is common in borderline tumors of the ovary.