Author/Editor		Volavšek, Metka; Glavač, Damjan; Gale, Nina
Title		Cell cycle regulating genes and their protein expression in squamous cell carcinoma of the larynx and hypopharynx
Translated title		Spremembe genov in proteinov celičnega ciklusa pri ploščatoceličnem karcinomu grla in spodnjega žrela
Type		članek
Source		Zdrav Vestn
Vol. and No.		Letnik 71, št. Suppl 3
Publication year		2002
Volume		str. III-29-34
Language		eng
Abstract		Background. The major mechanisms involved in genomic instability during tumour progression are loss of heterozygosity (LOH) and microsatellite instability (MSI). The most frequently affected are the tumor suppressor genes (TSG). Alterations of cell cycle proteins contribute to the development and biologic behaviour of malignant tumours. Methods. In a prospective study we evaluated the distribution and prognostic significance of immunohistochemically detected proteins p53, p21, p16, Rb, and cyclin D1 in 101 squamous cell carcinomas of the larynx and hypopharynx (LHSCC). Additionally, non isotopic MSI and LOH analysis was performed with microsatellite markers on chromosomes 3p, 9p, 17p, and 11q. Immunohistochemical and molecular alterations were compared to tumour grade, disease stage and three year patients overall and disease free survival. Results. Of 101 patients, there were 94 men and 7 women with 73 laryngeal and 28 hypopharyngeal cancers. Immunohistochemical staining was performed on all tumours and molecular analysis in 77 patients. In LHSCC, varying patterns of protein expression were found. A significant correlation was found between cyclin D1 and p21, cyclin D1 and Rb expression, and Rb expression and tumour grade. p53 and p16 expression did not correlate with other proteins. p16 expression correlated with LOH at 9p21, and LOH at 11q13 (cyclin D1 region) correlated with the tumour grade. We observed a high incidence of LOH at specific chromosomal regions: 3p (61%), 9p (54.4%), 17p (57.1%) and 11q (19.5%). Conversely, MSI was present in 6.5% of cases. In addition to tumour grade and N stage, only cyclin D1 expression revealed independent prognostic value for overall, but not disease free survival after multivariate analysis. Conclusions. In conclusion, our studydemonstrated the derailment of the growth promoting and suppressing pathways of cell cycle control in almost all LHSCC. (Abstract truncated at 2000 characters).
Summary		Izhodišča. Ploščatocelični karcinom (PKGV) glave in vratu je eden pomembnejših vzrokov zbolevnosti in smrtnosti zaradi malignih bolezni. Za zgodno odkrivanje in uspešno zdravljenje je pomembno tudi poznavanje molekularno genetskih mehanizmov, ki sodelujejo v razvoju PKGV. Dosedanje raziskave so pokazale, da sta pomembna mehanizma v razvoju malignih tumorjev izguba heterozigotnosti (IH) in mikrosatelitna nestabilnost (MSN). Spremembe povzročata v tumorje zavirajočih genih (TZG) in onkogenih. Pomen teh molekularno genetskih sprememb pri PKGV, ki se kažejo tudi kot spremenjeno izražanje beljakovinskih pridelkov genov, še ni povsem pojasnjen. Zato smo iskali pri ploščatoceličnem karcinomu grla in spodnjega žrela (PKGŽ) spremembe TZG p53, p21, p16 in Rb, domnevnega TZG FHIT ter onkogena ciklin D1 in ugotavljali njihovo razporeditev, diagnostični in napovedni pomen. Vsi našteti geni razen FHIT so udeleženi pri uravnavanju celičnega cikla, ki je pri malignih tumorjih porušeno. Metode. V prospektivno raziskavo smo vključili 101 bolnika, ki so bili od 1996 do julija 1999 kirurško zdravljeni zaradi ploščatoceličnega karcinoma grla in/ali spodnjega dela žrela. V vseh tumorskih vzorcih smo ocenili stopnjo diferenciranosti PKGŽ in imunohistokemično določili prisotnost beljakovinskih pridelkov genov p53, Rb, p21, p16 in ciklin D1. Iz operacijskih vzorcev smo ločeno odvzeli tumorsko in okolno, makroskopsko nespremenjeno tkivo, izolirali DNK in določili IH ter MSN. Uporabili smo mikrosatelitne označevalce za kromosome 3p, 9p, 17p in 11q. Spremembe smo primerjali s stopnjo diferenciacije tumorjev, razširjenostjo bolezni in njenim kliničnim potekom v prvih treh letih po začetku zdravljenja. Rezultati. Med 101 bolniki je bilo 94 moških in 7 žensk z operativno odstranjenim tumorjem grla v 73 in tumorjem spodnjega žrela v 28 primerih. (Izvleček prekinjen pri 2000 znakih).
Descriptors		LARYNGEAL NEOPLASMS CARCINOMA, SQUAMOUS CELL GENES, CDC SEX FACTORS AGE FACTORS DISEASE-FREE SURVIVAL IMMUNOHISTOCHEMISTRY DNA PRIMERS SURVIVAL ANALYSIS