Clinical and molecular prognostic factors in operable laryngeal cancer.
Many factors affect the prognosis in operable laryngeal squamous cell carcinoma (LSCC). Many clinical factors have been implicated in tumor recurrence and poor survival of the patients. The aim of the present study is to investigate the demographic, clinical and histological characteristics as prognostic factors. Moreover, our aim is to analyze the role of modern molecular biomarkers in the prognosis of patients with LSCC. One hundred patients with operable laryngeal carcinoma underwent surgery as primary treatment between April 1999 and April 2002. Ninety-four of them were men and 6 women, with a median age of 62 years (39-77). All demographic data of the patients were recorded. Staging of the tumor revealed 20 cases with T2 cancer, 46 cases with T3 and 34 cases with T4, while N classification included 91 patients with N0 tumor, 3 with N1 and 6 with N2. Among the 100 cases, 47 were located in the glottis, 46 in the supraglottic region and 7 were transglottic. Histology grading revealed 35 cases of grade G1, 50 cases of G2 and 15 cases of G3. Postoperatively, all patients were followed regularly for the possibility of tumor relapse, with a median follow-up period of 40.2 months (4.8-58.4). During the operation, a tissue specimen was collected from the tumor. The specimens were used for RNA and DNA extraction. Isolated RNA was used to investigate the expression of wt-p53, bcl-2, VEGF and EGFR by the reverse transcriptase PCR method (RT-PCR) using specific primers, while genomic DNA was used for the detection of EBV and HPV (16/18 subtypes) by the consensus primer-mediated polymerase chain reaction method (PCR). All data such as tumor recurrence and survival were recorded. Statistical analysis was performed using the SPSS and STATA statistical packages in order to investigate the role of all clinical and molecular factors and their combinations as significant prognostic markers. The tumor recurrence rate was 31%, while the tumor associated death rate was 27% and total death rate 30%. Univariate analysis for overall survival showed significance for the T stage, TNM stage and site of the tumor. Univariate analysis for the time to progression showed significance for the T stage, N stage, TNM stage, site of the tumor and tumors simultaneously positive for EGFR and VEGF, while EGFR expression was borderline insignificant. Multivariate analysis revealed TNM stage as the only significant factor for overall survival, and TNM stage, site of the tumor and EGFR expression as significant factors for time to progression. The molecular biomarkers EGFR and VEGF have a prognostic significance in laryngeal cancer in addition to the established clinical prognostic factors such as the stage and site of the tumor. These markers, apart from their role in carcinogenesis, seem to play an important role in tumor relapse.
Vlachtsis
Konstantinos
K
Department of Otorhinolaryngology Head and Neck Surgery, AHEPA Hospital, Aristotle University of Thessaloniki, Greece. kostis@med.auth.gr
Nikolaou
Angelos
A
Markou
Konstantinos
K
Fountzilas
George
G
Daniilidis
Ioannis
I
D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000401:mortality*; D018076:DNA, Complementary / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D007822:Laryngeal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification; D011379:Prognosis; D012334:RNA, Neoplasm / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D018076:DNA, Complementary; D004273:DNA, Neoplasm; D012334:RNA, Neoplasm; D042461:Vascular Endothelial Growth Factor A
Anticancer Res. 2000 Nov-Dec;20(6C):4863-6
11205233
Cancer. 1998 Jan 15;82(2):286-91
9445184
Am J Surg. 1996 Sep;172(3):263-6
8862080
J Pathol. 1999 Apr;187(5):549-55
10398120
Eur Arch Otorhinolaryngol. 1994;251(7):418-22
7857630
Laryngoscope. 1994 Jan;104(1 Pt 1):95-8
8295465
Anticancer Res. 2000 Sep- Oct;20(5B):3555-64
11131662
Anticancer Res. 2002 Jul-Aug;22(4):2089-96
12174888
Am J Epidemiol. 1997 Jun 15;145(12):1100-5
9199539
J Surg Oncol. 1991 Oct;48(2):87-95
1921404
Head Neck. 2003 Jan;25(1):67-73
12478546
Acta Otolaryngol. 1999;119(6):732-8
10587010
Eur Arch Otorhinolaryngol. 2003 Nov;260(10):549-54
14551784
Eur J Cancer. 1999 Feb;35(2):231-7
10448265
Clin Otolaryngol Allied Sci. 2000 Feb;25(1):23-7
10764233
Eur Arch Otorhinolaryngol. 1999;256(2):78-82
10068895
Laryngoscope. 2001 Jun;111(6):1079-87
11404625
Eur Arch Otorhinolaryngol. 1999;256 Suppl 1:S56-9
10337529
Arch Otolaryngol Head Neck Surg. 1999 Apr;125(4):417-22
10208679
Otolaryngol Head Neck Surg. 1998 Nov;119(5):548-53
9807091
Clin Cancer Res. 2002 Nov;8(11):3445-53
12429633
Int J Oncol. 2000 Dec;17(6):1099-105
11078794
Eur Arch Otorhinolaryngol. 2004 Feb;261(2):61-7
12856129
Virchows Arch. 1995;427(3):277-81
7496597
Otolaryngol Head Neck Surg. 1990 Nov;103(5 ( Pt 1)):805-12
2126104
Cancer. 2001 Aug 1;92(3):556-68
11505400
Laryngoscope. 2002 Apr;112(4):700-7
12150527
Oncology. 2002;63 Suppl 1:6-16
12422050
Cancer Res. 2000 Jul 1;60(13):3599-604
10910074
ORL J Otorhinolaryngol Relat Spec. 2000 May-Jun;62(3):143-8
10810259
Cancer. 1999 Feb 1;85(3):591-9
10091732
Laryngoscope. 1998 May;108(5):764-8
9591560
Otolaryngol Head Neck Surg. 2001 May;124(5):556-60
11337662
Arch Otolaryngol Head Neck Surg. 1997 Apr;123(4):412-9
9109790
N Engl J Med. 2001 Dec 27;345(26):1890-900
11756581
Laryngoscope. 2003 Jan;113(1):167-72
12514403
Br J Cancer. 1996 Oct;74(8):1253-7
8883413
Clin Cancer Res. 2000 Nov;6(11):4171-5
11106228
Ann Otol Rhinol Laryngol. 1995 Jul;104(7):503-10
7598360
Br J Cancer. 2000 Sep;83(6):775-81
10952783
Head Neck. 2002 Aug;24(8):792-9
12203806
Am J Otolaryngol. 1998 Mar-Apr;19(2):83-8
9550437
Oncologist. 2002;7 Suppl 4:16-24
12202784
Int J Cancer. 2003 Jun 10;105(2):273-80
12673691
Head Neck. 1998 Jan;20(1):16-21
9464947
Cancer. 1998 Jun 1;82(11):2159-65
9610695
Am J Surg. 1989 Oct;158(4):314-7
2802033
Laryngoscope. 2000 Jun;110(6):1012-7
10852523
Anticancer Res. 1999 Jan-Feb;19(1B):703-7
10216480
Int J Cancer. 1999 Apr 20;84(2):188-91
10096253
Clin Otolaryngol Allied Sci. 1998 Feb;23(1):57-62
9563667
Head Neck. 2001 Aug;23(8):629-36
11443745
Head Neck. 1997 Jul;19(4):323-34
9213111
Eur Arch Otorhinolaryngol. 2003 Oct;260(9):502-8
12736744
HNO. 2002 Jan;50(1):35-42
11963785