p16 inactivation in small‐sized lung adenocarcinoma: Its association with poor prognosis

Abstract

p16, an inhibitor of cell cycle machinery, is frequently inactivated in non-small cell carcinoma of the lung (NSCCL).To clarify the significance of p16 inactivation in the progression of lung adenocarcinoma, we immunohistochemically evaluated p16 protein status and Rb, p53 and cyclin D1 expression in 51 surgically resected adenocarcinomas that were less than 3 cm in diameter (median follow-up period: 52.5 months). Twenty-one of 51 adenocarcinomas showed negative immunostaining for p16. Twenty adenocarcinomas were also negative for Rb, while 31 and 13 were positive for p53 and cyclin D1, respectively. Loss of p16 expression was significantly correlated with scar grade, lymphatic permeation, lymph node metastasis and clinical stage. Rb protein expression was also inversely correlated with scar grade, pleural involvement and vascular invasion. When the cases were stratified according to the expression of both proteins, the Rb؊/p16؊ subset (7/51) consisted of poorly differentiated adenocarcinoma with a higher grade of invasion. While Rb, p53 and cyclin D1 protein status showed no significant correlations with prognosis, p16 inactivation was significantly correlated with poor prognosis, and the prognosis of Rb؊/ p16؊ was the worst among the 4 subsets. Inactivation of p16 may play a role in accelerating scar formation and lymph node metastasis, and may contribute through these mechanisms to poor prognosis in patients with small-sized lung adenocarcinoma.

Papillary adenocarcinoma of the lung is a more advanced adenocarcinoma than bronchioloalveolar carcinoma that is composed of two distinct histological subtypes

“…Expression of the p16 gene is decreased by hypermethylation of the promoter region and LOH at chromosome 9p21 in accord with the multiple-step progression of lung adenocarcinoma, and these alterations are closely associated with poor prognosis. [23][24][25][26][27] In adenocarcinoma of the lung, diffuse and strong p53 expression suggested that the p53 gene mutation is inversely correlated with tumor differentiation. 27 According to the results of these immunohistochemical data, PA seems to be a more advanced phenotype than BAC.…”

Inactivation of p16INK4a by CpG hypermethylation is not a frequent event in colorectal cancer

“…One study has shown an association between upregulation of expression and a well-differentiated phenotype in colorectal cancer [23]. Furthermore, loss of p16 expression has been associated with a poorly differentiated phenotype in other malignancies [13,15,19,50]. A possible reason for this association is that tumors with loss of p16 expression have deregulated cell cycle progression and this in turn may lead to rapid cell turnover.…”

“…Loss of p16 expression is an important step in promoting carcinogenesis as clearly evidenced by its association with a number of malignant diseases [11][12][13][14][15][16][17][18]. Importantly, loss of p16 expression has been associated with clinical stage, grade, and prognosis in some cancers [13,[15][16][17][19][20][21]. Loss of p16 expression has also been described in colorectal cancer in both tumors and cell lines [11,[22][23][24]; however, the incidence and clinicopathological significance of absent p16 expression in colorectal cancer have not been determined.…”

Μελέτη των διαταραχών του μεταγραφικού παράγοντα Pokemon στο μη μικροκυτταρικό καρκίνο του πνεύμονα

“…Οι αλλοιώσεις αυτές θεωρούνται πρώιμες στην καρκινογένεση του πνεύμονα[23,154]. Ο προγνωστικός ρόλος του δεν είναι πλήρως αποσαφηνισμένος[155,156].…”