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Classic and Molecular Cytogenetic Analyses Reveal Chromosomal Gains and Losses Correlated with Survival in Head and Neck Cancer Patients

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Classic and Molecular Cytogenetic Analyses Reveal Chromosomal Gains and Losses Correlated with Survival in Head and Neck Cancer Patients Vol. 11, 621–631, January 15, 2005 Clinical Cancer Research 621 Classic and Molecular Cytogenetic Analyses Reveal Chromosomal Gains and Losses Correlated with Survival in Head and Neck Cancer Patients Na´dia Aparecida Be´rgamo,1 that acquisition of monosomy 17 was a significant (P = Luciana Caricati da Silva Veiga,1 0.0012) factor for patients with a previous family history of Patricia Pintor dos Reis,4 Ineˆs Nobuko Nishimoto,3 cancer. Conclusions: The significant associations found in this Jose´ Magrin,3 Luiz Paulo Kowalski,3 4 2 study emphasize that alterations of distinct regions of the Jeremy A. Squire, and Sı´lvia Regina Rogatto genome may be genetic biomarkers for a poor prognosis. 1Department of Genetics, Institute of Biosciences and 2NeoGene Losses of chromosomes 17 and 22 can be associated with Laboratory, Department of Urology, Faculty of Medicine, Sa˜o Paulo a family history of cancer. State University; 3Department of Head and Neck Surgery and Otorhinolaryngology, AC Camargo Hospital, Sa˜o Paulo, Brazil and 4Department of Cellular and Molecular Biology, Princess Margaret INTRODUCTION Hospital, Ontario Cancer Institute, University of Toronto, Toronto, Carcinomas of the head and neck represent the sixth most Ontario, Canada frequent cancer worldwide and f90% to 95% are squamous cell carcinomas. Tobacco and alcohol consumption are the ABSTRACT most important nongenetic risk factors associated with the Purpose: Genetic biomarkers of head and neck tumors development of head and neck squamous cell carcinomas could be useful for distinguishing among patients with (HNSCC; ref. 1). Estimated age-standardized rates per similar clinical and histopathologic characteristics but 100,000 for 1990 showed 12.8 men and 3.7 women of oral having differential probabilities of survival. The purpose of cavity and pharynx cancers and 6.5 men and 1.1 women for this study was to investigate chromosomal alterations in head laryngeal cancer for Tropical South America, compared and neck carcinomas and to correlate the results with clinical with 12.1 and 5.7 men, respectively, to oral cancer and and epidemiologic variables. pharynx and laryngeal cancers for all areas in the world (2). Experimental Design: Cytogenetic analysis of short-term Tropical South America has one of the world’s highest age- cultures from 64 primary untreated head and neck squamous standardized rates of head and neck carcinomas (2, 3). cell carcinomas was used to determine the overall pattern of Abnormal karyotypes have been reported in >250 cultured chromosome aberrations. A representative subset of tumors HNSCC (4). Karyotypes are often complex, with many was analyzed in detail by spectral karyotyping and/or numerical and unbalanced structural aberrations. The most confirmatory fluorescence in situ hybridization analysis. frequent losses involve chromosome arms 3p, 7q, 8p, 9p, 11q, Results: Recurrent losses of chromosomes Y (26 cases) 13p, 14p, 15p, 16p, and 18q and gains at 1q, 3q, 8q, and 15q and and 19 (14 cases), and gains of chromosomes 22 (23 cases), band 11q13. Among recurrent structural alterations, the most 8 and 20 (11 cases each) were observed. The most frequent common are 8q isochromosomes, 3p deletions, and the presence structural aberration was del(22)(q13.1) followed by rear- of homogeneously staining regions at 11q13 (5–15). Previous rangements involving 6q and 12p. The presence of specific cytogenetic studies have primarily been observational and have cytogenetic aberrations was found to correlate significantly been drawn from predominantly European and North American with an unfavorable outcome. There was a significant cohorts. In this present study, we have examined cytogenetic association between survival and gains in chromosomes 10 aberrations in the context of accompanying clinical variables (P = 0.008) and 20 (P = 0.002) and losses of chromosomes 15 such as anatomic sites, histology, stage, grade, treatment, and (P = 0.005) and 22 (P = 0.021). Univariate analysis indicated outcome. Moreover, this study comprises a typical Brazilian patient cohort comprising multiracial ethnicity and the additional risk factors associated with South American lifestyle. This Received 4/22/04; revised 9/30/04; accepted 10/11/04. unique patient cohort has allowed us to associate genomic Grant support: Conselho Nacional de Pesquisa (Distrito Federal, alterations with familial history of cancer and other prognostic Brazil); Coordenac¸a˜o de Aperfeic¸oamento de Pessoal de Nı´vel Superior factors in 67 consecutive head and neck tumors arising in a (Distrito Federal, Brazil); Fundac¸a˜o de Amparo a` Pesquisa do Estado de Sa˜o Paulo (Centro de Pesquisa Inovac¸a˜o e Difusa˜o, Sa˜o Paulo, Brazil); representative Brazilian patient population. and Canadian Cancer Society, National Cancer Institute of Canada. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked MATERIAL AND METHODS advertisement in accordance with 18 U.S.C. Section 1734 solely to Patients. Sixty-seven head and neck tumor samples were indicate this fact. obtained from the AC Camargo Hospital, Sa˜o Paulo, Brazil from Requests for reprints: Silvia Regina Rogatto, NeoGene Laboratory, 1994 to 1996. The patients were accrued consecutively and the Department of Urology, Faculty of Medicine, Sa˜o Paulo State University, CEP 18618-000, Botucatu, Sa˜o Paulo, Brazil. Phone: 55-14-38116271; inclusion criteria were no previous new histologic diagnosis of Fax: 55-14-38116271; E-mail: [email protected]. head and neck cancer and a tumor larger than 1 cm in size. Three D2005 American Association for Cancer Research. samples were excluded: an olfactory neuroblastoma (case 1), Downloaded from clincancerres.aacrjournals.org on September 30, 2021. © 2005 American Association for Cancer Research. 622 Chromosomal Aberrations in Head and Neck Tumors Table 1 Description of cases according to age, gender, histopathological diagnosis, TNM status, clinical data and composite karyotype Case no. Sex/age Location Tumor grade TNM Affected relative/tumor site(s) Tobacco usage Nasal cavity 1 F/60 Nasal cavity 1 T1N0M0 Father/pancreas À Oral cavity 2y F/70 Maxillary antrum 1 T4N0M0 ÀÀ 3 M/47 Maxillary antrum 1 T4N0M0 ÀÀ 4y M/63 Oral mucosa 1 T4N0M0 À + 5 M/52 Tongue 1 T2N0M0 Uncle/prostate and bowel + 6 M/68 Tongue 1 T3N0M0 Sister/breast + 7 M/39 Tongue 1 T3N0M0 ÀÀ 8 F/87 Tongue 1 T3N1M0 Brother/lung À 9 M/57 Tongue 1 T3N2aM0 À + 10 M/64 Tongue 1 T4N0M0 ÀÀ 11y M/61 Tongue 1 T4N0M0 Two sisters/kidney + 12 M/58 Tongue 1 T4N1M0 À + 13 M/67 Tongue 1 T4N2bM0 À + 14y F/40 Tongue 2 T1N1M0 À + 15 M/53 Tongue 2 T2N0M0 ÀÀ 16y M/35 Tongue 2 T4N0M0 Cousin/stomach À 17 M/56 Tongue 2 T4N2aM0 À + 18 M/54 Tongue 2 T4N2aM0 À + 19y M/40 Tongue 4 T4N2aM0 Father/esophagus + 20 M/38 Gingiva 1 T4N0M0 À + 21 M/64 Gingiva 1 T4N2M0 ÀÀ 22 M/58 Gingiva 2 T4N0M0 À + 23 M/49 Floor of mouth 1 T2N0M0 À + 24y M/66 Floor of mouth 1 T4N0M0 À + 25 M/46 Floor of mouth 1 T4N2cM0 À + 26y F/74 Floor of mouth 2 T2N0M0 ÀÀ 27y M/63 Floor of mouth 2 T2N0M0 Brother/US À 28 F/50 Floor of mouth 2 T2N3M0 À + 29 M/53 Floor of mouth 1 T3N0M0 + 30 M/66 Floor of mouth 3 T3N1M0 À + 31 M/53 Retromolar 1 T3N1M0 Grandmother/stomach Uncle/larynx + 32 M/39 Retromolar 1 T4N2aM0 À + 33 M/58 Retromolar 2 T3N0M0 À + 34 F/61 Retromolar 2 T4N0M0 À + 35* M/65 Retromolar 2 T4N2sM0 À + Pharygeal carcinomas 36 M/71 Tonsil 1 T4N0M0 À + 37 M/42 Tonsil 1 T4N0M0 À + 38* M/56 Tonsil 2 T3N2cM0 Mother/uterus Father/bowel + 39 M/62 Tonsil 2 T4N2aM0 ++ 40 M/55 Tonsil 3 T4N1M0 À + 41 M/44 Oropharynx 1 T4N0M0 ÀÀ 42 M/48 Oropharynx 3 T4N0M0 À + 43 M/58 Pyriform sinus 2 T2N0M0 À + 44 M/32 Pyriform sinus 2 T3N0M0 À + 45 M/45 Pyriform sinus 2 T3N3M0 Sisters/breast Aunts/breast + 46 M/61 Pyriform sinus 2 T3N3M0 Grandmother/bowel + 47 M/61 Pyriform sinus 3 T4N3M0 Uncle/pharynx + Laryngeal carcinomas 48z M/62 Epiglottis 1 T3N0M0 À + 49y M/57 Epiglottis 1 T3N2cM0 À + 50 M/50 Supraglottis 3 T4N1M0 À + 51 M/67 Larynx 1 T3N0M0 À + 52 M/67 Larynx 1 T3N0M0 À 53 M/69 Larynx 1 T3N0M0 À + 54 M/70 Larynx 1 T3N2cM0 À 55 M/50 Larynx 1 T4N0M0 À + 56 M/49 Larynx 1 T3N0M0 Mother/bowel Ca + 57* M/65 Larynx 1 T4N0M0 À + 58y M/79 Larynx 2 T3N0M0 À + (Continued on the next page) Downloaded from clincancerres.aacrjournals.org on September 30, 2021. © 2005 American Association for Cancer Research. Clinical Cancer Research 623 Table 1 Description of cases according to age, gender, histopathological diagnosis, TNM status, clinical data and composite karyotype (Cont’d) Alcohol usage Follow-up* (mo) Composite karyotype based on ISCN guidelines (1995) À DOD (16) 41-47,X,ÀX,+8,+12,À17,À22,+mar [cp15]/46,XX[2] À DOD (18) 43-49,XX,+5,+8,+17,À19,À20,del(22)(q13.1),+mar[cp14]/46,XX [13] À Alive (24), lost to follow-up 41-47,XY,+6,+17,À20 [cp6]/46,XY[2] + Alive (15), lost to follow-up 41-48,X,ÀY,+9,add(9)(p24),+13,À18,À19,+22[cp21]/46,XY [8] + ANR (47) 46,XY[7] + ANR (36) 40-46,X,ÀY,À22[cp9]/46,XY[4] À AWC (41) 44-48,XY,+8,+22,+mar[cp4]/46,XY[5] À AWC (33) 43-48,X,ÀY,À3,+5,+7,+8,À19,À20,À21,À22 [cp12]/ 46,XY[4] + DOC (9) 44-47,XY,+10,del(11)(q23.3),del(12)(p12),+18,+20,À21,+22 [cp12]/46,XY [10] À DOD (29) 41-48,X,ÀY, À2,+8,À10,À14,+17,À22,+22 [cp18]/ 46,XY[5] + DOD (36) 42-48,XY,À10,del(10)(p13),+11,+18,+20,+del(22)(q13.1)[cp19]/ 46,XY[3] + DOD (12) 42-48,XY,À5,À13,+22[cp10]/46,XY[10] + DOD (3) 67-69,XXY,inc[28] À ANR (44) 43-47,X,ÀX,À21,+del(22)(q13.1)[cp9] /46,XX[20] À ANR (52) 41-47,X,ÀX,i(6p),+6,+7,+9,À11,À14,+?del(22)(q13.1),+mar[cp15]/ 46,XX[4] + DOD (6) 43-48,XY,À9,+10,À17,+22[cp15]
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