The prognostic significance of DNA ploidy in laryngeal cancers

Year 2002, Volume: 9 Issue: 6, 414 - 423, 20.12.2002

Timur Akçam Abdullah Akkaya Yalçın Özkaptan Mustafa Gerek Salih Deveci Önder Öngürü

Abstract

Objectives: We assessed the relationship betvveen DNA ploidy and histopathologic parameters and its effect on prog- nosis in patients with squamous celi carcinoma of the larynx.Patiaıts and Methods: Surgical sections of 44 patients who were treated for squamous celi carcinoma of the larynx were studied. Image cytometry measurements were performed on nuclear suspensions derived from paraffin-embedded sec­ tions to determine DNA ploidy patterns. We investigated the relationship betvveen the DNA ploidy status and localization, stage, differentiation, keratinization, depth of tumoral invasion, lymphocytic infiltration, perineural invasion, infiltration pattern, necrosis, and 5-year and overall survival rates.Results: Aneuploidy and diploidy were diagnosed in 65.9% and 34.1%, respectively. No significant relationships were found betvveen DNA ploidy and stage, localization, differentia­ tion, keratinization, depth of invasion, infiltration pattern, lym­ phocytic infiltration, necrosis, perineural invasion, and lymph node metastasis p>0.05 . The five-year p=0.048 and over­ all log rank=4.40; p=0.036 survival rates were significantly higher in diploid tumors. The presence of perineural invasion p=0.004 and depth of the invasion exceeding 9 millimeters p=0.045 were significant factors adversely influencing the five-year survival rate. The multivariate Cox regression analy- sis shovved that the DNA ploidy status p=0.042 and the pres­ ence of perineural invasion p=0.009 were independent prog­ nostic variables related to decreased survival.Conclusion: Aneuploidy has an adverse effect on the prognosis in squamous celi carcinoma of the larynx.

Keywords

Aneuploidy, carcinoma, squamous cell/pathology/ genetics/radiotherapy, DNA, neoplasm/analysis, diploidy, head and neck neoplasms/genetics, image cytometry, laryngeal neoplasms/ pathology/genetics, lymphatic metastasis, neoplasm recurrence, local, ploidies, prognosis, survival analysis

Larenks kanserlerinde DNA ploidinin prognostik önemi

Abstract

Amaç: Yassı epitel hücreli larenks kanseri olan olgulardaDNA ploidinin, tümöre ait özellikler ve histopatolojik parametreler ile iliflkisi ve prognoz üzerine etkisi arafltırıldı.Hastalar ve Yöntemler: Çalıflmada yassı epitel hücrelikanser nedeniyle tedavi edilip izlenen 44 olgunun cerrahikesitleri incelendi. Parafin bloklardan elde edilen nükleussüspansiyonlarında görüntü analizi tekniği ile DNA ploidiarafltırması yapıldı. DNA ploidinin tümör yerleflimi, evre,diferansiasyon, keratinizasyon, invazyon derinliği, lenfositinfiltrasyonu, perinöral invazyon, infiltrasyon türü, tümörnekrozu, befl yıllık sağkalım ve yaflam süresi ile iliflkisi değerlendirildi.B u l g u l a r : Olguların %65.9’unda anaploidi, %34.1’inde diploidi belirlendi. Tümör evresi, yerleflimi, diferansiasyon, keratinizasyon, invazyon derinliği, invazyon türü, lenfosit infiltrasyonu, tümör nekrozu, perinöral invazyon ve lenf nodu tutulumu ile DNA ploidi arasında anlamlı iliflki görülmedi p>0.05 . Diploid tümörlerde befl yıllık sağkalım p=0.048 ve genel sağkalım log rank=4.40; p=0.036 oranlarıanaploid tümörlere göre anlamlı düzeyde yüksek bulundu.Perinöral invazyon varlığı p=0.004 ve invazyon derinliğinin9 mm’nin üzerinde olması p=0.045 befl yıllık sağkalımı anlamlı düzeyde düflüren diğer faktörler olarak değerlendirildi.Cox regresyon analizi sonucunda DNA ploidi p=0.042 veperinöral invazyonun p=0.009 sağkalımı etkileyen bağımsız prognostik faktörler oldukları görüldü.Sonuç: Anaploidi varlığı, yassı epitel hücreli larenks kanserli olgularda prognozu olumsuz etkilemektedir

Keywords

Anaploidi, karsinom, skuamöz hücreli/patoloji/genetik/radyoterapi, DNA, neoplazm/analiz, diploidi, bafl-boyun neoplazmları/genetik, görüntü sitometrisi, larenjeal neoplazmlar/patoloji/genetik, lenfatik metastaz, neoplazm nüksü, lokal, ploidi, prognoz, sağkalım analizi

References

• Burgio DL, Jacobs JR, Maciorowski Z, Alonso MM, Pietraszkiewicz H, Ensley JF. DNA ploidy of primary and metastatic squamous cell head and neck cancers. Arch Otolaryngol Head Neck Surg 1992;118:185-7.
• Danic D, Milicic D, Prgomet D, Leovic D. Prognostic factors in carcinoma of the larynx: relevance of DNA ploidy, S-fractions and localization of the tumour. J Laryngol Otol 1999;113:538-41.
• Gandour-Edwards RF, Donald PJ, Yu TL, Howard RR, Teplitz RL. DNA content of head and neck squamous c a rcinoma by flow and image cytometry. Arc h Otolaryngol Head Neck Surg 1994;120:294-7.
• Myers EN, Sampedro A, Alvarez C, Martinez J, Suarez C, Alonso-Guervos M, et al. Cell proliferation activity and kinetic profile in the prognosis and therapeutic management of carcinoma of the pharynx and larynx. Otolaryngol Head Neck Surg 1999;121:476-81.
• Walter MA, Peters GE, Peiper SC. Predicting radiore s i s- tance in early glottic squamous cell carcinoma by DNA content. Ann Otol Rhinol Laryngol 1991;100:523-6.
• Friedlander ML, Hedley DW, Taylor IW. Clinical and biological significance of aneuploidy in human tumours. J Clin Pathol 1984;37:961-74.
• Auer GU, Caspersson TO, Wallgren AS. DNA content and survival in mammary carcinoma. Anal Quant Cytol 1980;2:161-5.
• Milroy CM, Ferlito A, Devaney KO, Rinaldo A. Role of DNA measurements of head and neck tumors. Ann Otol Rhinol Laryngol 1997;106:801-4.
• Feinmesser R, Freeman JL, Noyek A. Flow cytometric analysis of DNA content in laryngeal cancer. J Laryngol Otol 1990;104:485-7.
• Rua S, Comino A, Fruttero A, Cera G, Semeria C, Lanzillotta L, et al. Relationship between histologic features, DNA flow cytometry, and clinical behavior of squamous cell carcinomas of the larynx. Cancer 1991; 67:141-9.
• Cooke LD, Cooke TG, Forster G, Helliwell TR, Stell PM. Cellular DNA content and prognosis in surgically treated squamous carcinoma of the larynx. Br J Cancer 1991;63:1018-20.
• To ffoli G, Franchin G, Barzan L, Cernigoi C, Carbone A, S u l f a ro S, et al. Brief report: prognostic importance of cellular DNA content in T1 - 2N0laryngeal squamous cell c a rcinomas treated with radiotherapy. Laryngoscope 1 9 9 5 ; 1 0 5 : 6 4 9 - 5 2 .
• Westerbeek HA, Mooi WJ, Hilgers FJ, Baris G, Begg AC, Balm AJ. Ploidy status and the response of T1 glottic car- cinoma to radiotherapy. Clin Otolaryngol 1993;18:98-101.
• Kaplan AS, Caldarelli DD, Chacho MS, Bruce DR, Hutchinson J, Conway S, et al. Retrospective DNA analysis of head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 1986;112:1159-62.
• Goldsmith MM, Cresson DS, Postma DS, Askin FB, Pillsbury HC. Significance of ploidy in laryngeal can- cer. Am J Surg 1986;152:396-402.
• Stell PM. Prognostic factors in laryngeal carcinoma. Clin Otolaryngol 1988;13:399-409.
• Davis RK. Prognostic variables in head and neck cancer. Tumor site, stage, nodal status, diff e rentiation, and immune status. Otolaryngol Clin North Am 1985;18:411 - 9 .
• Rudoltz MS, Benammar A, Mohiuddin M. Pro g n o s t i c factors for local control and survival in T1squamous cell c a rcinoma of the glottis. Int J Radiat Oncol Biol Phys 1 9 9 3 ; 2 6 : 7 6 7 - 7 2 .
• Bryne M, Koppang HS, Lilleng R, Kjaerheim A. Malignancy grading of the deep invasive margins of oral squamous cell carcinomas has high prognostic value. J Pathol 1992;166:375-81.
• Kirita T, Okabe S, Izumo T, Sugimura M. Risk factors for the postoperative local recurrence of tongue carci- noma. J Oral Maxillofac Surg 1994;52:149-54.
• Fukano H, Matsuura H, Hasegawa Y, Nakamura S. Depth of invasion as a predictive factor for cervical lymph node metastasis in tongue carcinoma. Head Neck 1997;19:205-10.
• Onerci M, Yilmaz T, Gedikoglu G. Tumor thickness as a predictor of cervical lymph node metastasis in squa- mous cell carcinoma of the lower lip. Otolaryngol Head Neck Surg 2000;122:139-42.
• Sarioglu T, Yilmaz T, Sungur A, Gursel B. The effect of lymphocytic infiltration on clinical survival in cancer of the tongue. Eur Arch Otorhinolaryngol 1994;251:366-9.
• Yilmaz T, Hosal S, Gedikoglu G, Turan E, Ayas K. Prognostic significance of depth of invasion in cancer of the larynx. Laryngoscope 1998;108:764-8.
• Byers RM, O'Brien J, Waxler J. The therapeutic and pro g- nostic implications of nerve invasion in cancer of the lower lip. Int J Radiat Oncol Biol Phys 1978;4:215-7.
• Cottel WI. Perineural invasion by squamous-cell carci- noma. J Dermatol Surg Oncol 1982;8:589-600.
• Frierson HF Jr, Cooper PH. Prognostic factors in squa- mous cell carcinoma of the lower lip. Hum Pathol 1986; 1 7 : 3 4 6 - 5 4 .
• Goepfert H, Dichtel WJ, Medina JE, Lindberg RD, Luna MD. Perineural invasion in squamous cell skin carcinoma of the head and neck. Am J Surg 1984; 148:542-7.
• Soo KC, Carter RL, O'Brien CJ, Barr L, Bliss JM, Shaw HJ. P rognostic implications of perineural spread in squa- mous carcinomas of the head and neck. Laryngoscope 1 9 8 6 ; 9 6 : 11 4 5 - 8 .
• Kaya S, Ataman M, Sennaroğlu L, Gököz A. Bafl boyun kanserlerinde perinöral invazyonun prognoza etkileri. Turkish J Cancer 1992;22:21-4.
• Erdamar B, Suoglu Y, Kiyak E. Current trends and future prospects in biological markers in squamous cell carcinoma of the head and neck. [Article in Turkish] Kulak Burun Bogaz Ihtis Derg 2002;9:301-3.
• Anwar K, Nakakuki K, Imai H, Naiki H, Inuzuka M. Over-expression of p53 protein in human laryngeal carcinoma. Int J Cancer 1993;53:952-6.
• Boag G, Lee CS, Charalambous D, Rode J. p53 expres- sion in laryngeal carcinoma. Pathology 1993;25:394-7.
• Basut O, Erisen L, Coskun H, Erturk A, Tezel I. The relationship between mutant p53 and clinicopatholog- ic parameters in squamous cell carcinoma of the head and neck. [Article in Turkish] Kulak Burun Bogaz Ihtis Derg 2000;7:42-5.
• S p a ff o rd MF, Koeppe J, Pan Z, Archer PG, Meyers AD, Franklin WA. Correlation of tumor markers p53, bcl-2, CD34, CD44H, CD44v6, and Ki-67 with sur- vival and metastasis in laryngeal squamous cell car- cinoma. Arch Otolaryngol Head Neck Surg 1996;122: 6 2 7 - 3 2 .
• Sapçı T, Filizel F, fiensu S, Karavufl A, Karavufl M, Ertek S, ve ark. Larenksin skuamoz hücreli karsinom- larında “proliferating cell nuclear antigen”in prognos- tik önemi. KBB Bafl Boyun Cerrahisi Dergisi 1995; 3:173-81.
• Dobros W, Rys J, Niezabitowski A, Olszewski E. The prognostic value of proliferating cell nuclear antigen (PCNA) in the advanced cancer of larynx. Auris Nasus Larynx 1998;25:295-301.
• Sarac S, Ayhan A, Hosal AS, Kaya S. Prognostic signif- icance of PCNA expression in laryngeal cancer. Arch Otolaryngol Head Neck Surg 1998;124:1321-4.
• Liu M, Lawson G, Delos M, Jamart J, Chatelain B, Remacle M, et al. Prognostic value of cell pro l i f e r a t i o n markers, tumour suppressor proteins and cell adhesion molecules in primary squamous cell carcinoma of the larynx and hypopharynx [Published online: 24 July 2002]. Eur Arch Otorhinolaryngol DOI 10.1007/s00405- 002-0512-8. Available from: URL: http://link.springer. d e / l i n k / s e r v i c e / j o u r n a l s / 0 0 4 0 5 / c o n t e n t s / t f i r s t . h t m .
• Golusinski W, Olofsson J, Szmeja Z, Biczysko W, Krygier-Stojalowska A, Kulczynski B. A comprehen- sive analysis of selected diagnostic methods with respect to their usefulness in evaluating the biology of neoplastic cells in patients with laryngeal cancer. Eur Arch Otorhinolaryngol 1999;256:306-11.