THE EXPRESSION OF Bcl-2 AND PRO-CASPASE 3 IN HEAD AND NECK SQUAMOUS CELL CARCINOMA
Background. Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer and accounts for 6% of cancers worldwide. A better understanding of its biology could lead to improved treatment options. Generally, the goal of cancer treatment is to abolish cell proliferation and to induce necrotic or aptoptotic cell death. Apoptosis has been recognized as a key mechanism of tumour cell elimination. Different apoptotic signals converge to induce caspase cascade activation. Caspase 3 is the central executioner caspase and is necessary for effective apoptotic cell death. Bcl-2 protein family regulates apoptosis. The Bcl-2 protein itself is a product of a proto-oncogene and has an antiapoptotic action.
Methods. In our study, the expression of Bcl-2 and pro-caspase 3 by immunohistochemistry in 28 HNSCC graded into well, moderately and poorly differentiated cancers were investigated.
Results. Our results of Bcl-2 expression confirm and extend previous reports in which Bcl-2 over-expression has been recognised as an important parameter in HNSCC biological behaviour. Three of 28 tumours (11%) showed significant Bcl-2 expression. Two of them were poorly and one was moderately differentiated. Pro-caspase 3 immunoreactivity was confined mainly to the cytoplasm. Absent or low pro-caspase 3 immunoreactivity was found only in 1 of 6 well differentiated and in 1of 10 moderately differentiated tumours in contrast to 5 of 12 poorly differentiated tumours. In six of 12 poorly differentiated tumours procasapse 3 immunoreactivity was strongly positive. In two cases hyperplastic epithelium was strongly positive in contrast to adjacent HNSCC in the same slide which was completely negative for pro-caspase 3.
Conclusions. Our results indicate downregulation of pro-caspase 3 expression, especially in poorly differentiated HNSCC. Further studies are needed to test whether this is related to HNSCC behaviour and predict treatment outcome.
Condon LT, Ashman JNE, Ell SR, Stafford ND, Greenman J, Cawkell L. Overexpression of Bcl-2 in squamous cell carcinoma of the larynx: a marker of radioresistence. Int J Cancer 2002; 100: 472–5.
Cör A, Pajer Z. Apoptoza-programirana celična smrt in tumorji. Zdrav Vestn 1994; 63: 521–4.
Estrow Z, Thall PF, Talpaz M et al. Caspase 2 and caspase 3 protein level predictors of survival in acute myelogenous leukaemia. Blood 1998; 92: 3090–7.
Fisher DE. Apoptosis in cancer chemotherapy: crossing the threshold. Cell 1994; 78: 539–42.
Friedman M, Grey P, Vankatesen TK et al. Prognostic significance of bcl-2 expression in localized squamous cell carcinoma of the head and neck. Ann Otol Rhinol Laryngol 1997; 106: 445–50.
Fujikawa K, Shiraki K, Sugimoto K et al. Reduced expression of ICE/ Caspase1 and CPP32/Caspase3 in human hepatocellular carcinoma. Anticancer Res 2000; 20: 1927–32.
Gallo O, Boddi V, Calzolari A, Simonetti L, Trovati M, Bianchi S. Bcl-2 protein expression correlates with recurenceand survival in early stage head and neck cancer treated by radiotherapy. Clin Cancer Res 1996; 2: 261–7.
Hall PA. Assessing apoptosis: a critical survey. Endocr Relat Cancer 1999; 6: 3–8.
Hengartner MO. The biochemistry of apoptosis. Nature 2000; 407: 770–6.
Hočevar-Boltežar I, Žargi M. Voice quality after radiation therapy for early glotic cancer. Arch Otolaryngol Head Neck Surg 2000; 126: 1097–100.
Homma A, Furuta Y, Oridate N et al. Correlation of clinicopathological parameters and biological markers related to apoptosis and proliferation activity with a clinical outcome in squamous cell carcinoma of the larynx treated with concurrent chemoradiotherapy. Auris Nasus Larynx 2001; 28: S87–S94.
Hoshi T, Sasano H, Kato K et al. Immunohistochemistry of caspase3/CPP32 in human stomach and its correlation with cell proliferation and apoptosis. Anticancer Res 1998; 18: 4347–54.
Ioachim E, Assimakopoulous D, Agnatis NJ, Peschos D, Zissi A, Skevas A. Altered patterns of retinoblastoma gene product expression in benign, premalignant and malignant epithelium of the larynx: An immunohistochemical study including correlation with p53, bcl-2 and proliferating indices. AntiCancer Res 1999; 19: 541–6.
Izban KF, Wrone-Smith T, His ED et al. Characterization of the interleukin1 b-converting enzyme/Ced-3-family protease, caspase3/CPP32, in Hodgkin’s disease. Am J Pathol 1999; 154: 1439–47.
Jackel MC, Dorudian MA, Marx D, Brinck V, Schauer A, Steiner W. Spontaneous apoptosis in laryngeal squamous cell carcinoma is independent of Bcl2 and Bax protein expression. Cancer 1999; 85: 591–9.
Kaufmann SH, Hengartner MO. Programed cell death: alive and well in the new millennium. Trends Cell Biol 2001; 11: 526–33.
Kroemer G. The pro-oncogene bcl-2 and its role in regulating apoptosis. Nature Med 1997; 3: 614–20.
Nicholson DW. From bench to clinic with apoptosis-based therapeutic agents. Nature 2000; 407: 810–6.
Pižem J, Cör A. Kaspaze. Med Razgl 2001; 40; 283–291.
Shanmugaratnam K. WHO: Histological typing of tumours of the upper respiratory tract and ear. 2nd edition. Berlin: Springer-Verlag, 1991.
Strasser A, O’Conner L, Dixit WM. Apoptosis signalling. Int J Cancer 2000; 69: 217–45.
Takata T, Tanaka F, Yamada T et al. Clinical significance of caspase-3 expression in pathologic-stage I, nonsmall-cell lung cancer. Int J Cancer 2001; 96: 54–60.
Vakkala M, Paakko, Soini Y. Expression of caspases 2, 6, and 8 is increased in parallel with apoptosis and histological aggressiveness of the breast lesion. Br J Cancer 1999; 81: 592–9.
Whisler LC, Wood NB, Caldarelli DD et al. Regulators of proliferation and apoptosis in carcinoma of the larynx. Laryngoscope 1998; 108: 630–8.
Winter RN, Kramer A, Borkowski A, Kyprianou N. Loss of caspase-1 and caspase-3 protein expression in human prostate cancer. Cancer Res 2001; 61: 1227–32.
Yuen AP, Lam KY, Choy JT, Ho WK, Wei WI. The clinicopathological significance of bcl-2 expression in the surgical treatment of laryngeal carcinoma. Clin Otolaryngol 2001; 26: 129–33.
The Author transfers to the Publisher (Zdravniški vestnik/Slovenian Medical Journal) all economic copyrights following form Article 22 of the Slovene Copyright and Related Rights Act (ZASP), including the right of reproduction, the right of distribution, the rental right, the right of public performance, the right of public transmission, the right of public communication by means of phonograms and videograms, the right of public presentation, the right of broadcasting, the right of rebroadcasting, the right of secondary broadcasting, the right of communication to the public, the right of transformation, the right of audiovisual adaptation and all other rights of the author according to ZASP.
The aforementioned rights are transferred non-exclusively, for an unlimited number of editions, for the term of the statutory
The Author can make use of his work himself or transfer subjective rights to others only after 3 months from date of first publishing in the journal Zdravniški vestnik/Slovenian Medical Journal.
The Publisher (Zdravniški vestnik/Slovenian Medical Journal) has the right to transfer the rights, acquired parties without explicit consent of the Author.
The Author consents that the Article be published under the Creative Commons BY-NC 4.0 (attribution-non-commercial) or comparable licence.