The role and prognostic value of apoptosis in colorectal carcinoma

Julia Alcaide, Rafael Funez, Antonio Rueda, Elisabeth Perez-Ruiz, Teresa Pereda, Isabel Rodrigo, Rafael Coveñas, Miguel Muñoz, Maximino Redondo, Julia Alcaide, Rafael Funez, Antonio Rueda, Elisabeth Perez-Ruiz, Teresa Pereda, Isabel Rodrigo, Rafael Coveñas, Miguel Muñoz, Maximino Redondo

Abstract

Background: Alterations to apoptosis are a common occurrence in human tumours. The aim of our study was to determine the influence of apoptotic variations on the carcinogenesis and prognosis of colorectal carcinomas (CRCs).

Methods: A TUNEL assay was performed on archival material from 103 colorectal carcinomas, 26 adenomas and 20 samples of normal epithelia.

Results: The number of apoptotic cells was higher in CRCs (1.09 ± 0.13) than in adenomas (0.38 ± 0.23, p = 0.059) and normal epithelium (0.06 ± 0.04, p = 0.001). In addition, the apoptotic index (AI) was greater in metastatic disease (stage IV) than in other stages (p = 0.017). No relationship was found between apoptotic rates and age, gender or tumour grade. However, patients with tumours that showed higher AI values had a significantly lower disease-free survival (DFS) and overall survival (OS) than those with tumours that had lower AIs (p = 0.020 and p = 0.027). In a multivariate Cox proportional hazards model, AI remained a significant independent predictor of survival.

Conclusions: We conclude that disregulated apoptosis is an important event during CRC development and progression. Higher AIs are associated with more aggressive tumours and a poorer prognosis for patients with CRC.

Figures

Figure 1
Figure 1
Apoptosis detected by TUNEL assay. Positively stained cells were very scarce in normal mucosa (A), increased in adenomatous polyps (B) and especially in adenocarcinomas of the colon (C). Magnification, 200x (A), 400x (B, C).
Figure 2
Figure 2
The disease-free survival (DFS) of patients, grouped by apoptotic cell rates. The survival of patients with primary tumours presenting high AIs (lower line) is significantly shorter than the survival of patients presenting tumours with low AIs (upper line).
Figure 3
Figure 3
The disease-free survival (DFS) of patients with advanced-stage tumours (stages III and IV), grouped by apoptotic cell rates. Patients with high AIs (lower line) present shorter survival durations than patients with low AIs (upper line).

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