Proliferation Rate Ki-67 Research Articles

Diagnostic and prognostic value of Ki67 proliferation fraction in serous effusions.

The Ki67 proliferation rate of mesothelial cells was determined in 20 effusions due to malignant mesotheliomas and in 20 non‐neoplastic effusions, to investigate if this marker may be useful to identify neoplastic mesothelioma cells and if there is a correlation between proliferation rate and survival time. Using the ABC‐method, effusions were immunostained and the marker Ki67 was evaluated quantitatively. Ki67 proliferation fraction showed rates from 2.3% to 70% in malignant mesothelioma cells and from 1.8% to 25.5% in reactive mesothelial cells. A significant difference was found (p=0.05) between those two groups. Assuming a threshold at 26%, a sensitivity of 25% and specificity of 100% resulted. Yet, due to its low sensitivity this marker seems not to be useful for differential diagnosis. Plotting surviving period against Ki67 proliferation fraction a correlation was observed which was not significant. Long term survivors (>28 month) showed proliferation rates below 3.8%. Unexpectedly a highly significant difference (p=0.001) between Ki67 proliferation rates of mesothelial cells from patients with malignant tumors other than mesothelial origin (7.0% to 25.5%) and mesothelial cells of patients without any malignant disease (1.8% to 16.3%) were observed. Setting a threshold at 10% for identification of a malignant disease, a sensitivity of 77.8% and specificity of 90.9% resulted.

Ki-67 and p53 Expression in Minimal Deviation Melanomas as Compared with Other Nevomelanocytic Lesions

Minimal deviation melanoma is a controversial entity encompassing a heterogeneous group of lesions cytologically in the spectrum between recognized subtypes of nevi and conventional “primary configuration” melanomas and reported to have a better prognosis than the latter. To evaluate the distinctiveness of minimal deviation melanoma, Ki-67 proliferation rates and p53 expression in minimal deviation melanomas were compared with those in compound nevi, Spitz nevi, and vertical growth phase superficial spreading malignant melanoma. Twelve examples of each lesion were immunostained with antibodies to the Ki-67 and p53 proteins and evaluated by a pathologist who was blind to the diagnoses. The mean Ki-67 (MIB-1) proliferation rates for the compound nevi, Spitz nevi, minimal deviation melanomas, and superficial spreading malignant melanomas were 0, 3%, 13%, and 25%, respectively. The mean Ki-67 proliferation rate was statistically greater in the minimal deviation melanomas than in the compound nevi or the Spitz nevi (P < .05), but the proliferation rates in the two melanoma subtypes were not statistically significant (P = .08). The mean p53 values for these lesions were 0, 9%, 9%, and 26%, respectively; the latter two were statistically different (P < .01). Based on these Ki-67 and p53 immunophenotypes, minimal deviation melanoma may represent a distinct entity.

Estrogen receptors in prolactinomas: a clinico-pathological study.

Antiestrogens are effective in the treatment of estrogen receptor (ER) positive breast carcinoma. The use of antiestrogen therapy in pituitary adenomas, however, has not been explored. This study attempted to identify a population who may benefit from antiestrogen therapy. Prolactinomas from 29 patients (10 men, 19 women) were analyzed for ER and Ki-67 labeling index using immunohistochemistry. Nine of the 19 women were either amenorrheic or had not received exogenous estrogen for at least one year. Ten women were menstruating either spontaneously or as a result of estrogen administration. Factors including age, serum prolactin level, tumor size, evidence of tumor invasiveness and recurrence of tumor were evaluated to determine if they were predictive of ER expression. Tumors from 6/10 (60%) men were positive for ER. Among women who were having menses, 9/10 (90%) tumors were positive, whereas 6/9 (67%) tumors from amenorrheic women were positive. Statistical analysis revealed that none of the variables: gender, age, menstrual status, Ki-67 proliferative rate, exposure to dopamine agonists, preoperative prolactin level, tumor size, or invasiveness was predictive for the presence of the receptor. The incidence of ER, however, was significantly reduced in recurrent tumors (p = 0.03). ER expression is less likely in recurrent tumors. The efficacy of ER antagonists cannot be inferred by gender or estrogen exposure.

Pregnancy: Proliferative activity in ectopic trophoblastic tissue

Clinical observations have shown that tubal pregnancies develop individually different biological activities such as different growth rates, levels of beta human chorionic gonadotrophin (beta-HCG), or rates of tubal wall destruction. In the present study, we evaluated the proliferative activity of ectopic cytotrophoblastic tissue using immunocytochemistry with antibodies to Ki-67 (clone MIB-1). The rates of proliferation obtained were related to the maternal serum beta-HCG values. Reference data were obtained from placentas of intact intrauterine pregnancies (group I, n = 14). The proliferative activity of this tissue was compared to that of cytotrophoblastic tissue of tubal pregnancies (group II, n = 27). Ki-67-immunostained as well as non-stained cytotrophoblastic nuclei of the villi and the trophoblastic columns were counted separately, and results were expressed as percentage of positive cells. Serum beta-HCG values were determined twice, 48 h and immediately before operation. The cytotrophoblastic cells of intact intrauterine pregnancies (group I) showed uniform and high proliferative activities (80% on average in villi, 84% on average in columns). The average Ki-67 proliferation rate was significantly lower (P < 0.001) in trophoblastic tissue of tubal pregnancies (group II; 42% on average in villi, 61% on average in columns). Within the group of tubal pregnancies, higher intragroup differences were observed. The number of Ki-67-labelled cells was independent of the absolute preoperative serum beta-HCG values in both groups, yet they were clearly related to the relative increase of beta-HCG in maternal serum. At higher proliferation rates, there was a significant, growing increase of beta-HCG values (P < 0.01). We have found immunohistochemical evidence to support the previous clinical speculations that tubal pregnancies develop more heterogeneously and more slowly than intact intrauterine pregnancies. The development of the beta-HCG concentrations may be taken as an indirect parameter, reflecting proliferative activity of the trophoblast.

Detection of Ki-67 Proliferation Rate in Breast Cancer: Correlation with Clinical and Pathologic Features

In situ determination of proliferative activity was performed on 203 breast cancers by use of Ki-67 monoclonal antibody and immunohistochemical methods. Tumor proliferation rate was analyzed and correlated to tumor size and nodal status. The relationship between Ki-67 proliferative activity and nuclear estrogen receptor content was also investigated on adjacent tissue sections. Ki-67 values ranged from 1 to 75%, with a median value of 10%. Premenopausal patients had greater Ki-67 values (median value, 14.1%) than postmenopausal ones (median value, 9.8%). The authors observed no correlation with lymph nodal involvement, whereas a statistically significant relationship with tumor size was found (P less than 0.01). An inverse correlation (Spearman's coefficient = -0.56; P less than 0.001) was seen between Ki-67 values and nuclear estrogen receptor content. These results, similar to those reported for other kinetic measurements, suggest that in situ detection of Ki-67 proliferation rate is a useful method for obtaining cell cycle information. Follow-up studies will be needed to assess an eventual prognostic relevance.