Prognostic evaluation of proliferative activity and DNA content in the phyllodes tumor of the breast: immunohistochemical and flow cytometric study of 118 cases.

The goal of this study was the prognostic evaluation of histology, mitotic rate, S-phase fraction (SPF) and expression of proliferative antigen Ki67 and p53 protein in phyllodes tumor of the breast. The study was performed in the group of 118 patients with phyllodes tumor treated by surgery from 1952 to 1998. Mitotic rate was assessed on the representative histological specimens. Expressions of Ki67 and p53 were evaluated by immunohistochemistry on a section from the corresponding paraffin blocks which were also used for flow cytometric DNA evaluation. Histologically, 52 tumors were benign (LGM), 24 borderline malignancies (BM) while among 42 malignant tumors, 20 were monomorphous (HGM) and the remaining 22 revealed heterologic elements (HGH). Tumor recurrencies occurred in 17 patients, predominantly during the first three years after surgery, and 13 patients died of the tumor (1 BM, 12 both malignant variants). Multivariate analysis demonstrated mitotic rate, SPF and p53 expression as independent prognostic parameters for the disease-free survival. Histological tumor type and expression of Ki67 influenced independently the overall survival. In conclusion, the histological type of tumor phyllodes forms the basis for the prognosis of clinical outcome, but the indicators of the proliferative activity, especially Ki67 index, are valuable prognostic factors among patients with malignant variant of phyllodes tumor of the breast. Expression of the p53 protein in tumor cells could be also useful when the percentage of cells and intensity of expression are considered.

Prognostic significance of telomerase activity in soft tissue sarcomas.

Only few reports on the prognostic significance of telomerase activity in human cancer exist. To find a new prognostic marker in soft tissue tumors, we investigated 60 soft tissue sarcomas of different histology and six benign tumors for telomerase activity. Telomerase activity was measured by using the non-radioactive PCR-based TRAP-assay. PCR products were analyzed on an automated fluorescence sequencer. Tumors of grade-II and grade-III histology showed a significantly poorer prognosis. Both disease-free (p<0.03) and the overall survival (p<0.02) were reduced in the highly malignant sarcoma patients. We found telomerase activity in 38.3% of the cases, there being a correlation with a more aggressive behavior of soft tissue sarcomas. Telomerase activity correlated with the grade of malignancy (p=0.04), but not with sex (p=0.64) or age (p=0. 48) of the patients. The total survival was significantly reduced in patients with telomerase-positive sarcomas (p=0.04). Both of the patients having grade I tumors with telomerase activity died of disease, whereas 10 of 11 patients with telomerase-negative grade I tumors are still alive. Only one of the benign tumors showed telomerase activity. We suggest that telomerase activity is a potential prognostic factor in malignant soft tissue tumors. Despite the histological heterogeneity of soft tissue tumors, single entities should be assessed for telomerase activity.

Prognostic evaluation of cutaneous malignant melanoma: a clinicopathologic and immunohistochemical study.

BACKGROUND AND OBJECTIVES: Depth of invasion and stage of the disease are established prognostic indicators in cutaneous malignant melanoma. The role of other parameters is still an open problem. METHODS: In 93 consecutive patients with cutaneous malignant melanoma, the level of invasion, tumor thickness, ulceration, vascular invasion, lymphoplasmocytic infiltrates, and mitotic index were evaluated by histology. Expression of Ki-67 and PCNA proliferative antigens together with vimentin, S100, and HMB 45 proteins were assessed by immunohistochemistry. RESULTS AND CONCLUSIONS: Disease-free and overall survival were correlated with tumor stage, tumor thickness, level of invasion, macroscopic pattern, ulceration, vascular invasion, expression of HMB 45, PCNA, and Ki-67/MIB1. Stage, HMB 45, and PCNA were independent prognostic factors for disease-free survival, whereas tumor stage, tumor thickness, and expression of both proliferative antigens influenced overall survival independently. The variables studied demonstrated reciprocal correlation; therefore, analysis of many prognostic parameters in malignant melanoma could be recommended.

Prognostic assessment of histologic parameters in breast carcinomas: a prospective study.

A group of 350 unselected breast cancer patients, treated at the Center of Oncology in Cracow, Poland, between January 1992 and December 1994, was analyzed. The following reciprocally interrelated histologic characteristics were evaluated: 1) histologic tumor type (considered in 3 categories of aggressivity), 2) tumor grade (according to Scarf-Bloom-Richardson), 3) constituent of in-situ carcinoma in invasive cancers and characterization of breast lobuli, 4) tumor growth pattern (microfocal, macrofocal or mixed), 5) invasion of nerves, 6) vascular invasion by cancer cells in tumor surroundings, 7) extensiveness of tumor necrosis, 8) involvement of the breast distant from the tumor mass by cancer cells, 9) status of axillary lymph nodes, 10) invasion of metastatic lymph node surroundings. Metastases in axillary lymph nodes were independently influenced by vascular invasion in tumor surroundings and tumor diameter. The disease-free survival was independently influenced by tumor diameter, necrosis and stage of the disease (pTNM), whereas total survival related to tumor diameter, nodal status, microfocal pattern of tumor growth, vascular invasion and involvement of breast by cancer distant from the tumor mass was independently influenced only by tumor stage (pTNM).

Sarcomatoid carcinoma (carcinosarcoma) of the gallbladder.

We report a case of carcinoma of the gallbladder in a 67-year-old woman. The description comprises the histological, immunohistochemical, ultrastructural and cytogenetical picture of the tumor. The ultrastructural features as well as chromosomal changes may denote the epithelial derivation of the tumor studied.

Assessment of proliferative activity, DNA values and some clinicopathologic parameters in mesenchymal tumors. Immunohistochemical and flow cytometric study.

Clinicopathologic parameters of 70 consecutive mesenchymal tumors from 63 patients were evaluated. In all these cases, the DNA content was analyzed by flow cytometry, and the expression of proliferative antigen MIB1 and p53 protein was assessed by immunohistochemistry. Our study verified the prognostic usefulness of proliferative indicators, above all MIB1-index, which strongly correlated with tumor grade and independently influenced overall survival.

Relationship of histology, DNA-values and proliferative activity in unselected breast cancer patients (a preliminary study).

Based upon a group of 108 consecutive mammary carcinomas a comparative analysis of morphological parameters, DNA-ploidy and indicators of proliferation activity was made. A correlation between Bloom-Richardson scale, mitotic index, PCNA-labeling index and DNA-index was shown. The ploidy of mammary carcinomas was significantly related to the values of proliferative fraction, as well as to PCNA-labeling index. Among patients with axillary metastases the tumor size and the value of PCNA-labeling index were significantly higher than those in patients with negative lymph nodes.

Flow cytometric evaluation of Ki67 proliferative antigen in primary breast cancer.

In the group of forty five primary mammary carcinomas Ki67 reactivity was evaluated with flow cytometry and immunohistochemistry. The expression of proliferative antigen, evaluated with both methods did not correlate with other indicators of proliferative activity. This result is probably associated with the physicochemical properties of breast cancer cells.

Comparative flow cytometric DNA analysis on fresh and paraffin-embedded tumor tissue in different neoplasms.

The results of flow cytometric DNA-analysis on fresh and paraffin-embedded tissue were compared in four various groups of tumors. The best correlation of the results was observed in the group of non Hodgkin's lymphomas. Comparative analysis of the ploidy on fresh and paraffin embedded tissue demonstrated discordance in particular in mammary carcinoma and malignant melanoma groups. The values of proliferative fraction assessed on fresh and paraffin embedded tissues were interrelated.

Alveolar soft part sarcoma: an analysis of 8 cases. Review of the literature.

Eight cases of alveolar soft part carcinoma (ASPS) are presented. The average age of the patients was 28 years. There were 6 women and 2 men. The left sided and right sided tumours were equal in number. Local recurrence was not observed in any of the patient treated, but lung metastases occurred in 6 of them. Three patients died with disease the average 35 months after treatment. Histologically in one case the uniform sheets of cells were observed without alveolar arrangement. The presence of beta glucuronidase (BG), acid phosphatase (AP) and non specific esterase (NE) in tumor cells was seen in one case studied. Immunohistochemical and ultrastructural examination confirm the thesis, that ASPS consist a distinct clinico-morphologic entity, the histogenesis of which remains uncertain.