Comparison of PCNA/cyclin immunohistochemistry with flow cytometric S-phase fraction in breast cancer

Abstract

Kinetic index determined by enumeration of neoplastic cells positive for proliferative cell nuclear antigen (PCNA) in 70 breast carcinomas (avidin-biotin immunoperoxidase technique) was compared to synthesis-phase fraction (S-phase, or SPF) values obtained by flow cytometry (FCM) using a multiparametric, 2 color method (dual-label propidium iodide/cytokeratin-FITC). The percent PCNA positive tumor cells (12.5% mean, range 1-28%) was significantly greater in aneuploid tumors (14.2% mean, N = 35) compared to diploid range tumors (10.7% mean, N = 35) (p less than 0.05), and was correlated with SPF derived from ungated DNA histograms (12.5% mean +/- 5.5%, r = 0.45, p less than 0.001). Marginally stronger statistical correlations were observed between the PCNA index and SPF values calculated from cytokeratin-gated (15.8% mean, r = 0.53, p less than 0.001) DNA histograms or from SPF values obtained following linear baseline debris subtraction (mean = 8.1%, r = 0.48, p less than 0.001). Significant associations were identified between PCNA index and prognostically important clinicopathologic parameters including nuclear grade (p = 0.014), presence of necrosis (p = 0.005), and angiolymphatic invasion (p = 0.003). We conclude: 1) PCNA index is comparable to FCM SPF and correlates with factors of known prognostic importance in carcinoma of the breast; 2) baseline debris and contaminating events derived from non-epithelial cells both represent significant artifacts in proliferative fraction estimates derived from FCM DNA histograms; and 3) multiparametric analysis may represent one means of improving the specificity and clinical value of FCM SPF determinations.

Proliferating cell nuclear antigen (PCNA) in high‐grade malignant fibrous histiocytoma: Prognostic value in 48 patients

“…PCNA has been shown in different tumors to correlate well with KI-67 scores (Hall et al, 1990; Allegranza Fontanini et al, 1992), flow cytometric data (Dawson et al, 1990;Allegranza et al, 1991;Fontanini et al, 1992;Visscher et at., 1992), tritiated thymidine (Hall et al, 1990;Allegranza et al, 1991) and mitotic count (Lipponen and Eskelinen, 1992).…”

“…Most tumors are highly malignant; 2/3 of the patients progress to metastasis and death, usually within 2 years of diagnosis (Weiss and Enzinger, 1992; Rooser et al, 1991;Pezzi et al, 1992;Pritchard et al, 1993). Several prognostic factors have been identified, such as tumor size (Weiss and Enzinger, 1992; Rooser et al, 1991;Pezzi et al, 1992), depth (Pritchard et al, 1993), location (Weiss and Enzinger, 1992), age (Pritchard et al, 1993), grade (Becker et al., 1991;Pezzi et al, 1992), necrosis (Rooser et al, 1991), nuclear morphometrics (Becker et al, 1991) and specific chromosomal aberrations (Rydholm et al, 1990) but better prognostication is still needed.The fraction of tumor cells in S-phase determined by proliferating cell nuclear antigen (PCNA) analysis has been shown to be of prognostic value in several carcinomas (Jain et al., 1991; Woods et al, 1991;Yu et al, 1991;Klemi et al, 1992;Lipponen and Eskelinen 1992, Fontanini et al, 1992). Therefore, we examined the correlation between the fraction of PCNA-positive nuclei in the tumor and the outcome in 48 patients with MFH.…”

“…Several subtypes have been described, the storiform-pleomorphic and myxoid being the most common. Most tumors are highly malignant; 2/3 of the patients progress to metastasis and death, usually within 2 years of diagnosis (Weiss and Enzinger, 1992;Rooser et al, 1991;Pezzi et al, 1992;Pritchard et al, 1993). Several prognostic factors have been identified, such as tumor size (Weiss and Enzinger, 1992;Rooser et al, 1991;Pezzi et al, 1992), depth (Pritchard et al, 1993), location (Weiss and Enzinger, 1992), age (Pritchard et al, 1993), grade (Becker et al, 1991;Pezzi et al, 1992), necrosis (Rooser et al, 1991), nuclear morphometrics (Becker et al, 1991) and specific chromosomal aberrations (Rydholm et al, 1990) but better prognostication is still needed.…”

Proliferation markers in tumours: interpretation and clinical value.

“…Expression of PCNA correlates partly with other proliferation markers such as %S-phase fraction, [31][32][33] Ki67 staining, 34 and mitotic count. 32 Not all studies, however, have confirmed the correlation with mitotic count, 35 and the PCNA labelling index could not be correlated with the Ki67 labelling index.…”

Histological prognostic parameters for adenocarcinoma of the pancreatic head. Proposal for a scoring system for prediction of outcome

“…TN is reported to be an important prognostic factor for soft tissue sarcoma19,20 and breast cancer 21. The frequency of TN is significantly greater in highly proliferative than in weakly proliferative tumors 22. Therefore, it appears that the interaction between the tumor cells and stromal cells, and the degree of proliferative activity of the tumor cells, have a strong influence on the survival of patients with pancreatic adenocarcinoma.…”