The prognostic and predictive value of ERCC-1, p53, bcl-2 and bax in epithelial ovarian cancer.

AIM: To evaluate the expression of ERCC-1 in patients with epithelial ovarian cancer (EOC) and to correlate it with the expression of p53, bcl-2 and bax. MATERIALS AND METHODS: Tumor samples from 60 patients with EOC were immunohistochemically investigated for the expression of ERCC1, p53, bcl-2 and bax. RESULTS: ERCC-1 expression was significantly decreased in serous and endometrioid compared to clear cell carcinomas. P53 expression was significantly increased in serous compared to clear cell carcinomas. Bax expression was significantly increased in serous carcinomas as compared to MMTs. High disease stage was correlated with low ERCC-1 and high bcl-2 expression. ERCC-1 expression was associated with increased disease-free interval. CONCLUSION: ERCC-1 status seems to be correlated with disease-free interval, stage and tumor histologic subtype in patients with EOC. Nevertheless, our results indicate that single-gene expressions may be unreliable and thus caution is needed when used as potential prognostic or predictive markers.

Tumor dissemination after laparoscopic surgery for an unsuspected endometrial stromal tumor.

BACKGROUND: The use of laparoscopic surgery in gynecologic oncology might be complicated by unsuspected side-effects for the patient. Experimental data suggest that the risk of tumor dissemination in the non traumatized peritoneum may be higher after pneumoperitoneum than after laparotomy, and they also show the importance of the surgeon's experience and technique. CASES: We present two cases of uterine endometrial stromal tumors which were laparoscopically excised. In both cases, intraperitoneal tumor seedings were identified shortly after the initial operation. The first patient had a low-grade endometrial stromal sarcoma and succumbed from the disease two years after the initial operation, while the second patient who was diagnosed with endometrial stromal tumor remains disease free two years later. CONCLUSIONS: The laparoscopic excision of an endometrial stromal tumor might result in tumor dissemination into the abdominal cavity. A careful second-look examination of the abdomen or a radical surgical approach is proposed.

Intraoperative assessment of epithelial and non-epithelial ovarian tumors: a 7-year review.

OBJECTIVE: To determine the accuracy of frozen section diagnosis of ovarian tumors and to discuss discrepant diagnostic cases. METHODS: 932 ovarian tumors were submitted for frozen section examination. Cases with a significant diagnostic discrepancy between the intraoperative and the final histological diagnosis were reviewed. RESULTS: The sensitivity of frozen section diagnosis for benign, borderline and malignant epithelial tumors was 98.82%, 98.97% and 87.66% and the specificity 98.01%, 97.06% and 100%, respectively. There were 27 cases with diagnostic discrepancy. All non teratomatous sex cord/stromal and germ cell tumors were correctly diagnosed while a diagnostic discrepancy was observed in teratomatous tumors. CONCLUSION: Frozen section diagnosis is a reliable method for the surgical management of an ovarian mass. Nevertheless, care should be taken for large tumors measuring > 20 cm in diameter, particularly when the intraoperative diagnosis reveals an epithelial borderline tumor or a teratomatous tumor with an extensive neural component.

Endocervical glandular lesions: a diagnostic approach combining a semi-quantitative scoring method to the expression of CEA, MIB-1 and p16.

OBJECTIVES: To investigate whether combining a semi-quantitative scoring method with the immunohistochemical expression of CEA, MIB-1 and p16, would improve the diagnostic accuracy of endocervical glandular lesions. METHODS: The hematoxylin and eosin-stained sections of 95 cervical biopsies were examined by 4 different observers and were grouped into three categories, benign, dysplasia and adenocarcinoma in situ, depending on the degree of nuclear stratification, nuclear atypia and the number of mitosis and apoptotic figures. Each case was also stained immunohistochemically with antibodies against CEA, Ki-67 (MIB-1) and p16. Staining was graded as negative, weak and positive. The accuracy of the scoring method alone was compared to the accuracy of combining the score with the immunostaining results. RESULTS: Using the semi-quantitative scoring system, most of the cases that were initially diagnosed as atypical hyperplasia or tuboendometrial metaplasia fell into the benign category. This scoring system discriminates effectively (Kruskal-Wallis, p<0.001) between the three categories (benign, endocervical glandular dysplasia and adenocarcinoma in situ). When analyzing the immunohistochemical score, only Ki-67 staining seems to be effective mostly in discriminating between normal glands or glands with atypical hyperplasia and epithelial glandular dysplasia. Ki-67, CEA and p16 failed to discriminate between tuboendometrial metaplasia and epithelial glandular dysplasia. Combining the semi-quantitative scoring system with the immunohistochemical results discriminates between the three categories equally well as the semi-quantitative scoring system alone (Kruskal-Wallis, p<0.001). Nevertheless, the proportion of cases that were classified similarly to the prestudy diagnosis was higher when the combined score was used. CONCLUSIONS: Combining a semi-quantitative scoring scheme with the immunohistochemical expression of CEA, MIB-1 and p16 seems to be of value in classifying some endocervical glandular lesions.

Myoepithelial cell cocktail (p63+SMA) for the evaluation of sclerosing breast lesions.

Sclerosing breast lesions may sometimes mimic the appearance of infiltrating carcinoma due to the entrapment of ductular structures in a fibrotic core. The immunohistochemical detection of the outer myoepithelial cell layer that is indicative of a non-infiltrating lesion is a valuable clue for the diagnosis of such ambiguous cases. The myoepithelial cell markers smooth muscle actin (SMA) and p63 are most commonly used since their specificity and sensitivity are well established. However, recent studies have indicated that some morphologically distinct myoepithelial cells fail to stain for SMA and that p63 positivity can be rarely expressed by a subset of malignant epithelial cells. Moreover, SMA can also be positive in stromal myofibroblastic cells and normal vessels that can be found close to the entrapped ductules and might be erroneously interpreted as myoepithelial cells. In this study, we used a double-immunolabeling technique combining both SMA and p63 antibodies (myoepithelial cell cocktail), in order to investigate whether this technique is advantageous over either marker used alone, in diagnosing sclerosing breast lesions. Our results indicate that p63 alone is not a useful myoepithelial cell marker if applied in large sclerosing breast lesions, however, in smaller lesions it is still of high value. On the contrary, SMA proved significantly useful in the evaluation of myoepithelial cells in larger but not in smaller complex sclerosing lesions. The myoepithelial cell cocktail has a staining sensitivity identical to that of SMA. Nevertheless, in a certain number of cases the cocktail might be useful in differentiating myoepithelial cells from stromal myofibroblasts or vascular smooth muscle cells due to the false impression of a higher staining intensity of the cocktail resulting from the expression of both nuclear and cytoplasmic/membranous antibodies that occupy a wider area of the cell under control.

Multicentricity in renal cell carcinoma: can primary tumor location serve as a co-determinant of surgical treatment?

OBJECTIVE: To assess the incidence of multicentricity in our series of renal cell carcinoma (RCC) patients and to investigate whether certain clinicopathological parameters could assist the selection of the appropriate surgical modality. METHODS: We performed a retrospective analysis of 235 RCC specimens that had been resected by radical nephrectomy at our institution from June 1995 to 2001. RESULTS: Twenty-six (11%) kidneys contained at least one small accompanying nodule. Fourteen (6%) kidneys exhibited satellite tumors that were histologically consistent with the adenomas, while "true" multicentricity was detected in 12 (5%) specimens. In the latter, the number of concomitant foci was independent of the size of the primary tumor. No correlation was observed between histological pattern and multifocality. In five out of seven (71%) specimens that contained the main tumor mass within the upper or middle portion of the kidney, satellite lesions were found to be located at the mid-kidney, whereas specimens with lower-pole RCC demonstrated no restriction in the distribution of accompanying nodules. All patients had been screened pre-operatively by ultrasonography and CT scanning. CONCLUSIONS: Our findings may be suggestive of a putative link between primary tumor location and multicentricity, although this relation could not be statistically confirmed. The 5% incidence of multicentricity renders the biological significance of satellite adenomas and/or adenocarcinomas unclear.