G. Breitenecker

Accuracy of Intraoperative Frozen-Section Diagnosis in Stage I Endometrial Adenocarcinoma

The purpose of our study was to determine if frozen-section diagnosis accurately identified patients suffering from endometrial adenocarcinoma FIGO stage I for surgical staging consisting of total abdominal hysterectomy, bilateral salpingo-oophorectomy, peritoneal cytology, and complete bilateral pelvic lymphadenectomy in moderately differentiated tumors with myometrial invasion. In all poorly differentiated tumors, and in all tumors with deep myometrial invasion (more than 50%) surgical staging included additional para-aortic lymphadenectomy. We performed a retrospective study including 70 patients. Frozen-section diagnosis of myometrial invasion and tumor grade was compared with permanent-section diagnosis. The accuracy rates were determined, and compared with accuracy rates of frozen-section diagnosis in the literature, and a total accuracy rate for 624 patients suffering from stage I endometrial adenocarcinoma was evaluated. In our patient collective, the overall accuracy rate of frozen-section diagnosis for myometrial invasion and tumor grade was 80 and 84%, respectively. In the five comparable studies, the mean accuracy rate for myometrial invasion and tumor grade was 89 and 84%, respectively. In combination with the five comparable studies our recent study produced an accuracy rate of frozen-section diagnosis for myometrial invasion and tumor grade of 88 and 84% in 624 patients, respectively. Despite an accuracy level of frozen-section diagnosis for myometrial invasion of 80 and 84% for tumor grade in our patient collective, all patients who required surgical staging were accurately identified.

Serum concentration of pregnancy-specific beta-1-glycoprotein (sp-1) in normal and pathologic pregnancies.

SummaryIn 50 females with normal pregnancies serum concentrations of the pregnancy-specific protein SP-1 were assayed by single radial immunodiffusion (Mancini) from the 20th week of gestation onwards. The total of 283 single tests revealed that serum SP-1 concentrations steadily increased after the 20th week of gestation to reach a plateau in the 37th week.Single radial immunodiffusion failed to identify any SP-1 in umbilical cord blood of newborns.Serum SP-1 concentrations were also assayed in high-risk pregnancies: In cases with diabetes and Rh-incompatibility serum levels were within the normal range. In EPH gestoses with a favorable prognosis serum levels were usually below the means but still within the normal range. In EPH gestoses with a poor prognosis concentrations were found to be considerably lower and mostly fell below the 2S range.ZusammenfassungDie Serumkonzentration des schwangerschaftsspezifischen Proteins SP-1 wurde bei 50 Frauen mit normaler Schwangerschaft mittels der einfachen radialen Immundiffusionsmethode nach Mancini ab der 20. Woche geprüft. Aus insgesamt 283 Untersuchungen ergibt sich: die Konzentration von SP-1 steigt von der 20. Woche der Gestation kontinuierlich an, um ab der 37. Woche eine Plateaubildung zu erfahren.Durch die genannte Methode konnte im Serum des Nabelschnurblutes von Neugeborenen in keinem Fall SP-1 nachgewiesen werden.Die Serumkonzentration von SP-1 wurde bei Fällen mit Risikoschwangerschaften geprüft:Bei durch Diabetes und Rhesusinkompatibilität komplizierten Graviditäten lagen die Werte im Normbereich; Fälle von EPH-Gestose mit guter Prognose lagen im Normbereich, meist unterhalb der Mittelwerte; Fälle von EPH-Gestose mit schlechter Prognose zeigten massiv gesenkte Werte, zum Großteil unterhalb der doppelten Standardabweichung.

Prognostic value of CD44 splice variants in human stage III cervical cancer

The expression of specific cell adhesion molecule CD44 isoforms (splice variants) has been shown to be associated with poor prognosis in human malignancies, such as breast cancer. We used three different variant exon sequence-specific murine monoclonal antibodies to epitopes encoded by exons v5, v6 or v7-v8 of human variant CD44, to study the expression of CD44 splice variants by immunohistochemistry in human stage III cervical cancer. We investigated 40 pretreatment punch biopsies of cervical cancer FIGO stage III. CD44 splice variants CD44v5, CD44v6 and CD44v7-8 were detected by means of immunohistochemistry in 90%, 55% and 25%, respectively. CD44 epitopes encoded by exon v5 were not correlated with prognosis. Expression of CD44 splice variants containing epitopes encoded by exon v6 were correlated with significantly poorer prognosis (Mantel test, P = 0.008). Five-year survival rates with or without CD44v6 expression were 20% versus 71%, respectively. Expression of CD44v7-8 was also correlated with significantly poorer overall survival (Mantel test, P = 0.02). Expression of CD44 splice variants containing epitopes encoded by exons v7-v8 and especially exon v6 is associated with significantly poorer prognosis in stage III cervical cancer patients.

Prognostic value of immunohistochemically detected HER-2/neu oncoprotein in endometrial cancer

HER-2/neu (c-erbB-2) oncoprotein is a transmembrane glycoprotein and may function as a growth factor receptor being involved in the regulation of cell growth and cell transformation. We performed an analysis of 100 patients with endometrial cancer stage FIGO I to IV using an immunoperoxidase technique on formalin-fixed, paraffin-embedded tissue samples in order to determine HER-2/neu oncoprotein expression. HER-2/neu oncoprotein was expressed in the tumors of 21 patients (21%). Clinical stage, histologic stage, histologic grade and death of invasion did not correlate with HER-2/neu oncoprotein expression. We found HER-2/neu oncoprotein in all clinical stages and therefore it does not seem to be a late event in the natural history of endometrial cancer. HER-2/neu oncoprotein expression was associated with poor overall survival (log-rank P-value 0.04).

Immunohistochemical expression of laminin-5 in cervical intraepithelial neoplasia

OBJECTIVESnLaminin-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.nnnMETHODSnWe 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.nnnRESULTSnWe 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.nnnCONCLUSIONSnAccording 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.

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 turmors) 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.

IMMUNOHISTOCHEMICAL DIFFERENTIATION BETWEEN OVARIAN GRANULOSA CELL TUMORS AND OVARIAN CARCINOMAS

SummaryDifferential diagnosis is a major problem in histopathology of ovarian tumors. Difficulties may arise if the tumor is a poorly differentiated carcinoma or a granulosa cell tumor of the sarcomatoid type. It was the aim of the present study to evaluate the usefulness of immunohistochemistry in differentiating between granulosa cell tumors of the ovary and ovarian carcinomas. We investigated 56 ovarian malignancies (13 granulosa cell tumors, 17 serous, 14 mucinous and 12 poorly differentiated carcinomas) and performed immunohistochemical detection of Vimentin, Keratin, CA125, CA19-9, CEA, S100 and Ber-EP4. Expression of Vimentin was highest and expression of Keratin was lowest in granulosa cell tumors in contrast to carcinomas. CA125 and CA19-9 were not expressed in granulosa cell tumors, whereas the detection rate in carcinomas (except for CA125 in mucinous carcinomas) was high. CEA, S100 and Ber-EP4 do not seem to be useful markers in differential diagnosis. A marker profile of Vimentin, Keratin, CA125 and CA19-9 allows a quite strict differentiation between poorly differentiated ovarian carcinomas and granulosa cell tumors of the ovary.

Oral contraceptives and human papillomavirus infection in cervical intraepithelial neoplasia

SummaryWe report about 142 patients from whom colposcopically directed cervical punch biopsies were taken which showed condylomatous lesions with or without cervical intraepithelial neoplasia (CIN). Fiftysix (39.4%) of these women used oral contraceptives (OC) for at least two years before examination. We used DNA in situ hybridization on all biopsies for detection of human papillomavirus (HPV)-DNA. Among OC users a significant trend towards higher HPV infection rates in high grade CIN (odds ratio 2.9,P<0.05) was found, whereas non-users of oral contraceptives had the highest HPV infection rate in condylomatous lesions without CIN (odds ratio 0.5,P<0.05). Thus in OC users HPV infection was about 24 times more likely in CIN III as in condyloma, whilest among non-users the trend was the other way round (7-fold likelyhood of HPV positivity in condyloma compared to CIN III). Other known risk factors for cervical carcinoma did not influence HPV infection rates in either group.

CA19-9, CA125 and CEA in Endometrial Carcinoma Tissue and Its Relation to Hormone Receptor Content and Histological Grading -

SummarySamples of 40 endometrial carcinomas were examined by immunohistochemical methods for CA19-9, CA125 and CEA. CA19-9 was detected in 93%, CA125 in 65% and CEA in 58%. CA19-9 was detected in more than 50% of tumor cells in 14 cases and the same was true for CA125 in six cases. In no tumor was CEA found in more than half the cells. The distribution of CA125 and CEA was markedly more heterogenous than that of CA19-9. There was no statistically significant correlation between immunohistochemical markers on the one hand, and estrogen and progesterone receptor content on the other. A correlation between histological grading and marker detection was only found for CA19-9. CA19-9 was detected in almost all endometrial carcinoma samples, and was the most homogenously distributed. This makes CA19-9 a possibly useful tumor marker for endometrial carcinoma.

Diagnosis of cervical intraepithelial neoplasia and human papillomavirus infection: punch biopsy versus cervical smear

SummaryIn 102 patients referred to our colposcopy clinic because of one to three Papanicolaou smears indicating cervical intraepithelial neoplasia (CIN) and/or abnormal colposcopy, routine smears and colposcopically directed punch biopsies were taken simultaneously. For detection and typing of human papillomavirus (HPV)-DNA in situ hybridization was performed in all biopsies and in 46 of the cervical smears. In cases of dysplastic lesions the number of HPV 16/18 (40.5%) and 31/33 (42.9%) was markedly higher than HPV 6/11 (16.6%) infection rate. In cases where simultaneous in situ hybridization in biopsy specimen and cervical smears was performed 21.7% showed a HPV negative smear and a positive biopsy, in 6.5% the results were the other way round. In 34.9% of cases with CIN I and 9.5% of cases with CIN II verified by punch biopsy the cytological smear did not indicate dysplasia. Our data show that mild and moderate CIN lesions of the cervix as well as HPV infection are detected more frequently by a combination of cervical smear and colposcopically directed punch biopsy than by cervical smear alone.