Loss of 18q predicts poor survival of patients with squamous cell carcinoma of the head and neck

Tumor suppressor genes play an important role in normal growth regulation. Loss or inactivation of these genes has been implicated in the development of squamous cell cancer and progression of neoplasia. Previous studies in our laboratories have implicated chromosome 18 long‐arm deletions as a possi...

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Veröffentlicht in:Genes chromosomes & cancer 1998-04, Vol.21 (4), p.333-339
Hauptverfasser: Pearlstein, Richard P., Benninger, Michael S., Carey, Thomas E., Zarbo, Richard J., Torres, Frank X., Rybicki, Benjamin A., Van Dyke, Daniel L.
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container_end_page 339
container_issue 4
container_start_page 333
container_title Genes chromosomes & cancer
container_volume 21
creator Pearlstein, Richard P.
Benninger, Michael S.
Carey, Thomas E.
Zarbo, Richard J.
Torres, Frank X.
Rybicki, Benjamin A.
Van Dyke, Daniel L.
description Tumor suppressor genes play an important role in normal growth regulation. Loss or inactivation of these genes has been implicated in the development of squamous cell cancer and progression of neoplasia. Previous studies in our laboratories have implicated chromosome 18 long‐arm deletions as a possible marker of progression in head and neck squamous cell cancer (HNSCC). To test this hypothesis, we evaluated DNA from 67 HNSCC patients for loss of heterozygosity (LOH) at 18q loci, and for association of LOH with survival. Tumor and normal DNA were extracted from fresh tissue and paraffin blocks and were amplified by PCR using primers for three microsatellite repeat polymorphisms in 18q (D18S336, D18S34, and MBP). A total of 27 (40%) patients had LOH of 18q, and these patients had a statistically significantly poorer two‐year survival compared to those without 18q LOH (30% vs. 63%; P=0.008). In a Cox proportional hazards model in which time from diagnosis to death was the outcome variable, patients with 18q LOH had an unadjusted relative risk (RR) of death of 2.46 (P = 0.005). When 18q LOH was placed in a multivariate model controlling for possible confounders in the study, the RR for death was still elevated (RR = 2.10; P = 0.025). The observation of a prognostic association between 18q LOH and poor patient survival suggests that loss of an 18q tumor suppressor gene or genes is important in the progression of HNSCC. Genes Chromosomes Cancer 21:333–339, 1998. © 1998 Wiley‐Liss, Inc.
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Loss or inactivation of these genes has been implicated in the development of squamous cell cancer and progression of neoplasia. Previous studies in our laboratories have implicated chromosome 18 long‐arm deletions as a possible marker of progression in head and neck squamous cell cancer (HNSCC). To test this hypothesis, we evaluated DNA from 67 HNSCC patients for loss of heterozygosity (LOH) at 18q loci, and for association of LOH with survival. Tumor and normal DNA were extracted from fresh tissue and paraffin blocks and were amplified by PCR using primers for three microsatellite repeat polymorphisms in 18q (D18S336, D18S34, and MBP). A total of 27 (40%) patients had LOH of 18q, and these patients had a statistically significantly poorer two‐year survival compared to those without 18q LOH (30% vs. 63%; P=0.008). In a Cox proportional hazards model in which time from diagnosis to death was the outcome variable, patients with 18q LOH had an unadjusted relative risk (RR) of death of 2.46 (P = 0.005). When 18q LOH was placed in a multivariate model controlling for possible confounders in the study, the RR for death was still elevated (RR = 2.10; P = 0.025). The observation of a prognostic association between 18q LOH and poor patient survival suggests that loss of an 18q tumor suppressor gene or genes is important in the progression of HNSCC. 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Cancer</addtitle><description>Tumor suppressor genes play an important role in normal growth regulation. Loss or inactivation of these genes has been implicated in the development of squamous cell cancer and progression of neoplasia. Previous studies in our laboratories have implicated chromosome 18 long‐arm deletions as a possible marker of progression in head and neck squamous cell cancer (HNSCC). To test this hypothesis, we evaluated DNA from 67 HNSCC patients for loss of heterozygosity (LOH) at 18q loci, and for association of LOH with survival. Tumor and normal DNA were extracted from fresh tissue and paraffin blocks and were amplified by PCR using primers for three microsatellite repeat polymorphisms in 18q (D18S336, D18S34, and MBP). A total of 27 (40%) patients had LOH of 18q, and these patients had a statistically significantly poorer two‐year survival compared to those without 18q LOH (30% vs. 63%; P=0.008). 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subjects Carcinoma, Squamous Cell - genetics
Chromosome Deletion
Chromosomes, Human, Pair 18 - genetics
Female
Head and Neck Neoplasms - genetics
Humans
Loss of Heterozygosity
Male
Multivariate Analysis
Prognosis
Proportional Hazards Models
Survival Analysis
title Loss of 18q predicts poor survival of patients with squamous cell carcinoma of the head and neck
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