The prognostic significance of cell cycle markers in esophageal cancer after neoadjuvant chemotherapy

Abstract

Proliferating cell nuclear antigen (PCNA), p27 and cyclin A were analyzed by immunohistochemistry in 89 patients (untreated control n = 40, neoadjuvant chemotherapy n = 49) with esophageal cancer invading the submucosal lesion. The mitotic index (MI) was calculated as the percentage of mitotic cells. In control subjects, the mean PCNA, p27, cyclin A and MI were, respectively, 60.4%, 18.0%, 19.9% and 1.7%; in the chemotherapy group, these values were 46.8%, 15.1%, 18.0% and 1.2% respectively. Neoadjuvant chemotherapy decreased PCNA and the MI significantly. As prognostic indicators, PCNA and the MI were significant in control subjects and p27 and cyclin A were significant in the chemotherapy group. Using multivariate analysis, p27 was a prognostic factor in both groups and cyclin A was prognostic only in the chemotherapy group. Although PCNA and the MI were useful growth and prognostic markers in untreated control subjects, their significance was lost after neoadjuvant chemotherapy. p27 and cyclin A were determined to be significant markers in the neoadjuvant chemotherapy group, especially p27, which was independent in both groups.

Clinicopathological significance of cyclooxygenase-2 and cell cycle-regulatory proteins expression in patients with esophageal squamous cell carcinoma

“…For overall survival, multivariate analysis indicated that p27 expression was a significant independent prognostic factor. These results are concordant with Miyabe and Filipits's study in mucoepidermoid carcinoma and breast cancer 8–26 . Duncan's study suggested that cytoplasmic p27 expression, but not nuclear, was independently predictive of prognosis on multivariate analysis in ovarian carcinoma.…”

“…These results are concordant with Miyabe and Filipits's study in mucoepidermoid carcinoma and breast cancer. [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] Duncan's study suggested that cytoplasmic p27 expression, but not nuclear, was independently predictive of prognosis on multivariate analysis in ovarian carcinoma. This finding may reflect a more complex function of p27 within cell cycle regulation.…”

“…Those molecular markers were observed in 1000 cells at least at high power (×400), and their percent of positive cells was used to evaluate the expression condition of these markers. It was considered high expression when the nuclear staining was above 10% for cyclin A and Ki‐67 13,14 and when above 50% for p27 15 …”