Clinical relevance of expression of the CIP/KIP cell-cycle inhibitors p21 and p27 in laryngeal cancer.
OBJECTIVE
To investigate the prognostic relevance of p21 and p27 protein expression in laryngeal squamous cell carcinoma (LSCC).


METHODS
We have analyzed by immunohistochemistry p21 and p27 expression in a series of 132 patients who underwent surgical resection of their LSCC and who had previously been investigated for p53 gene mutations and cyclin D1 expression. The tumors were considered low expressors when they had </= 10% of p21 and </= 50% of p27 immunoreactive neoplastic cells.


RESULTS
In 41 cases (31.1%), p21 was expressed in </= 10% of neoplastic cells; in 91 cases (68.9%), it was expressed in more than 10% of neoplastic cells. In 11 cases (8.3%), p27 was expressed in less than 5% of neoplastic cells; in 39 cases (29.6%), it was expressed in 5% to 50% of neoplastic cells; and in 82 cases (62.1%), it was expressed in more than 50% of the neoplastic cells. Low levels of p21 expression were associated with poor histologic differentiation and lymph node metastases. Low levels of p27 expression were associated with tumor extension and advanced clinical stage. Expression of p21 and p27 was not correlated with p53 gene status, and low p27 expression was more frequently detected in the cyclin D1-positive cases, with a borderline level of statistical significance. At univariate analysis, anatomic site, tumor extension, clinical stage, high cyclin D1 expression, and low p27 expression were significantly associated with reduced disease-free and overall survival rates. At multivariate analysis, high cyclin D1 expression and low p27 expression were the only significant covariates. The patients with a cyclin D1(+)/p27(-) phenotype had the poorest disease-free and overall survival rates.


CONCLUSIONS
Our study provides evidence that the immunohistochemical evaluation of p27 expression is a significant independent predictor of prognosis in laryngeal carcinoma.
Pruneri
G
G
II Servizio di Anatomia Patologica, Clinica Otorinolaringoiatrica I, Laboratorio Epidemiologico, Istituto di Scienze Mediche, Università di Milano, Ospedale Maggiore di Milano, Milan, Italy.
Pignataro
L
L
Carboni
N
N
Buffa
R
R
Di Finizio
D
D
Cesana
B M
BM
Neri
A
A
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007822:Laryngeal Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D025521:Tumor Suppressor Proteins
D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D008869:Microtubule-Associated Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27