Prognostic significance of apoptosis and associated factors in oral squamous cell carcinoma

Abstract

Tumour progression is characterised by an imbalance between cell proliferation and apoptosis. The aim of our study was to estimate the importance of proliferation and apoptosis associated parameters in primary squamous cell carcinomas (SCCs) of the oral cavity and oropharynx. For determination of apoptosis, the enzymatic labelling of DNA fragmentation with a terminal transferase reaction was used in 156 tissue samples of 107 patients, including corresponding lymph-node metastases in nine cases. P53, bcl-2, and Ki-67 were determined immunohistologically. P53 was detectable in 50.5% of the cases. Positive staining was associated significantly with decreased apoptosis (P<0.003). Bcl-2 was upregulated in 31.8% of the cases depending on the tumour grading (P<0.001) and correlated negatively with apoptosis (P<0.001). Proliferation (P<0.006) and apoptosis (P<0.03) were enhanced in larger tumours, though a direct correlation between these two parameters was not proven. Nevertheless, in contrast to the conventional tumour staging and grading, neither the expression of p53 or bcl-2 nor the apoptosis or Ki-67 measurements were able to predict survival or recurrence-free survival of the patients suffering from a SCC in the oral cavity or oropharynx. Our observations suggest that the function of wild-type p53 to induce apoptosis is lost in at least half of the SCCs under study and that the physiological function of bcl-2 as potent inhibitor of apoptosis is widely preserved in oral SCC.

The expression of p53-induced protein with death domain (Pidd) and apoptosis in oral squamous cell carcinoma

“…The amount of apoptosis seen in carcinomas varied ( Figure 1B), with a range of apoptotic indices from 0.03 to 2.25%. The amount of apoptosis that we observed in the TUNEL assay was generally similar to that reported by others (Xie et al, 1999;Macluskey et al, 2000;Stoll et al, 2000). The late stages of apoptosis that result in the distinctive morphology of an apoptotic cell are thought to occur rapidly, followed by phagocytic removal of the apoptotic bodies by neighbouring cells.…”

“…Tumour cells can acquire resistance to apoptosis by various mechanisms that interfere at different levels of apoptosis signalling and involve both the death receptor and mitochondrial pathways (Igney and Krammer, 2002). Previous studies of apoptosis in OSCC have described a correlation between high AI and well-differentiated carcinomas (Xie et al, 1999) and between the antiapoptotic protein Bcl-2 and high histological grade (less differentiated carcinomas) (Jordan et al, 1996;Stoll et al, 2000). Our data indicate the opposite relationship of low AI in well-differentiated tumours, and provide an explanation for tumour cell accumulation in welldifferentiated carcinomas that have a low proliferation rate.…”

“…In previous studies that examined apoptosis and their markers in OSCC, the expression of anti-apoptotic proteins such as Bcl-2 was reported to be strongest in poorly differentiated carcinoma, whereas pro-apoptotic proteins such as Bax and high apoptotic index (AI) correlate with well-differentiated carcinoma (Jordan et al, 1996;Xie et al, 1999;Stoll et al, 2000). This would suggest that apoptosis has not been effectively evaded in well-differentiated, keratinising squamous cell carcinomas with low proliferative index (PI) and makes it difficult to account for the growth of these tumours.…”

G1/S-specific Cyclin-D1 Might be a Prognostic Biomarker for Patients with Laryngeal Squamous Cell Carcinoma

“…Several researches have focused on the significance of Ki-67 in squamous cell carcinoma of head and neck (Girod et al, 1998;Sittel et al, 1999;Stoll et al, 2000;Bettendorf and Herrmann, 2002;Carinci et al, 2002;Myoung et al, 2006). This heterogeneous result showed the correlation of Ki-67 expression to tumor phenotype factors.…”

Prognostic value of p53 mutations, bax, and spontaneous apoptosis in maxillary sinus squamous cell carcinoma

“…There are several reports showing no association between p53 overexpression and prognosis in laryngeal carcinoma [26][27][28] and in oral cancer. 57 In contrast to overexpression of p53, the mutation of p53 is likelier to be associated with an unfavorable clinical course in head and neck SCC. In advanced laryngeal carcinoma, Bradford et al 58 reported that p53 mutation is associated with a poor prognosis.…”