Expression of proliferating cell nuclear antigen, Ki‐67 antigen, estrogen receptor protein, and tumor suppressor p53 gene in cytologic samples of breast cancer: An immunochemical study with clinical, pathobiological, and histologic correlations

Abstract

Sixty-six unselected breast cancers were analyzed in cytologic smears and histologic sections for the expression of Ki-67, proliferating cell nuclear antigen (PCNA), estrogen receptor protein (ERP), and p53 protein using a standard immunochemical method. The results, expressed as both positive cases and labelling index (LI), were compared with clinical and pathobiological variables. Ki-67 and PCNA immunostaining was seen in all cases, whereas ERP was detectable in 46/63 cases and p53 protein in 20/66 cases. The expression of these markers was generally lower in cytology than in histology, though the differences were not statistically significant. PCNA-LI and Ki-67-LI were closely correlated (P < 0.001), the mean PCNA:Ki-67 ratio being 0.92 +/- 0.57. Occasional discrepancies, however, were found. PCNA and Ki-67 expression was associated with an increase in histologic grade and a decrease in ERP content of tumors, whereas p53 was statistically associated with no clinical or pathobiological variables. The data suggest that proliferative activity and oncogene overexpression may be reliably evaluated in breast cancer by FNA cytology, though PCNA is not a suitable indicator for cell proliferation. The results do not resolve the issue as to whether immunostaining for p53 protein constitutes a dedifferentiation product of the tumor, or is a fundamental aspect of the malignant progression. Survival studies in a larger series of tumors are thus needed to elucidate this point.

Expression of Proliferating Cell Nuclear Antigen (PCNA) in breast carcinoma and its association with Ki67 and tumor grade in mastectomy specimens

“…Similar results were identified by other authors also ( Pelosi G and Brown DC). [9,10] The Ki67 LI mean and median values agree with already reported values ranging from 7.2 to 32.4%, the highest median value of 32.4% was observed by study done by Caly M. [11] When tumor grade is high the resultant proliferative activity is also higher which is reflected by high LI of PCNA and Ki67. Our results indicate that high grade tumors follow uncontrolled proliferative activity as a mechanism of tumor progression.…”

“…Similar results were also obtained by Thomas et al and Surowik et al [14,15] who studied correlation of these two markers in good number of primary breast carcinomas, our results agree with their conclusions. But, these results contradict the data obtained by Pelosi G et al, Dawson et al and Battersby et al [9,16,17] who showed positive correlation between these two markers. However they applied different antibody lineage as well as used frozen sections in their study.…”

Correlation of p53 Mutations in ThinPrep-Processed Fine Needle Breast Aspirates with Surgically Resected Breast Cancers

“…Other studies examining the associ- ation between these clinical variables and p53 protein accumulation and/or mutations have yielded inconsistent and often conflicting results. For example, Caleffi et al found that p53 mutations occurred in younger patients (38) but other studies have not found an association between age and p53 status (5,39,40). The number of patients in the current report is small and may have compromised the statistical power of the study to detect associations.…”

p53 and Ki-67 expression in renal cell carcinomas of pregnant women and their correlation with prognosis: a pilot study

“…In addition, simultaneous overexpression of p53 and Ki-67 was reported in early stages of tumorigenesis (21) , while p53-negative and Ki-67-positive tumoral immunophenotypes were already associated significantly with an unfavorable outcome (22) . Finally, concerning the discrepancies between Ki-67 and PCNA immunopositivity, we know that the former antigen is expressed in all cycling cells, whereas the latter reveals only the S-phase fraction; differences between Ki-67 and PCNA scores were already described in breast cancer (23) , transitional cell carcinoma (24) , laryngeal epithelial lesions (25) , endometrial adenocarcinoma (26) , and oral leukoplakia (27) , being commonly accepted that Ki-67 seems to be more consistent for use in therapeutic clinical trials.…”