Expression of TGF-Alpha and c-fos in Conventional and Basaloid Squamous Cell Carcinoma of Floor of Mouth

Abstract

Basaloid squamous cell carcinoma of the floor of the mouth is a newly recognized variant of squamous cell carcinoma that has a very aggressive behavior. To characterize basaloid squamous cell carcinoma at the molecular level, the authors studied the immunohistochemical expression in this tumor of the oncogene c-fos and of transforming growth factor-alpha. Eight cases of basaloid squamous cell carcinoma were evaluated by immunoperoxidase staining and compared to 16 squamous cell carcinomas of the floor of the mouth that ranged from well to poorly differentiated. The expression of c-fos was stronger in basaloid squamous cell carcinoma and poorly differentiated squamous cell carcinoma than it was in well-differentiated squamous cell carcinoma. Conversely, transforming growth factor-alpha expression was much stronger in well-differentiated squamous cell carcinoma than in basaloid squamous cell carcinoma or poorly differentiated squamous cell carcinoma. Moderately differentiated squamous cell carcinomas showed weak to moderate immunostaining for transforming growth factor-alpha but stained intensely for c-fos, which was consistently expressed at a high level in these tumors. This study confirms the poorly differentiated nature of basaloid squamous cell carcinoma, which has a similar pattern of staining as poorly differentiated. The decreased expression of transforming growth factor-alpha in basaloid squamous cell carcinoma may be related to the low degree of differentiation of this tumor since transforming growth factor-alpha tends to have higher levels of expression in well-differentiated tumor cells. Int J Surg Pathol 3(3):169-174, 1996

Keywords

basaloid squamous cell carcinoma c-fos TGF-alpha cell differentiation.

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References

Wain LS , Kier R. , Vollmer RT , Bossen EH Basaloid-squamous carcinoma of the tongue, hypopharynx and larynx: Report of 10 cases. Hum Pathol 17:1158-1166, 1986

McKay MJ , Bilous AM Basaloid-squamous carcinoma of the hypopharynx . Cancer 66:537-542, 1990

Banks ER , Frierson HF , Mills SE , George E. , Zarbo RJ , Swanson PE Basaloid squamous cell carcinoma of the head and neck: A clinicopathologic and immunohistochemical study of 40 cases. Am J Surg Pathol 16:939-946, 1992

Coppola D. , Catalano E. , Tang CK , Elfenbein IB , Harwick R. , Mohr R. Basaloid squamous cell carcinoma of floor of mouth. Cancer 72:2299-305, 1993

Sassoni-Corsi P. , Sisson JC , Verma IM Transcriptional autoregulation of the proto-oncogene Fos. Nature 334:314-319, 1988

Ransone LJ , Verma IM

Nuclear proto-oncogenes Fos and Jun

Ann Rev Cell Biol 6:539-575, 1990

Willman CL , Fenoglio-Preiser M.

Oncogenes, suppressor genes, and carcinogenesis

Hum Pathol 18: 895-902,1987

Derynck R.

Transforming growth factor-alpha: Structure and biological activities

J Cell Biochem 32: 293-304, 1986

Wong ST , Winchell LF , McCune BK , Earp H. , Teixido J. , Massague J. , Herman B. , Lee DC. The TGF-alpha precursor expressed on the cell surface binds to the EGF on adjacent cells, leading to signal transduction. Cell 56:495-506, 1989

10.

Sakai Y. , Gray Nelson K. , Snydeker S. , Bossert NL , Walker MP , McLachlan J. , Diaugustine RP Expression of epidermal growth factor in suprabasal cells of stratified differentiation . Cell Growth Differ 5:527-535, 1994

11.

Basset-Seguin N. , Escot C. , Blanchard JM , Kerai C. , Verrier B. , Mion H. , Guilhou JJ High levels of c-fos proto-oncogene expression in normal human adult skin. J Invest Dermatol 94:418-422, 1990

12.

Basset-Seguin N. , Escot C. , Moles JP , Blanchard JM , Kerai C. , Guilhou JJ C-fos and c-jun proto-oncogene expression is decreased in psoriasis: An in situ quantitative analysis. J Invest Dermatol 97: 672-678, 1991

13.

Fisher C. , Byers MR , ladarola MJ , Powers EA Patterns of epithelial expression of fos protein suggest important role in the transition from viable to cornified cell during keratinization . Development 111:253-258, 1991

14.

Stone RM , Sariban E. , Pettit GR , Kufe DW Bryostatin 1 activates protein kinase C and induces monocytic differentiation of HL-60 cells. Blood 72: 208-213, 1988

15.

Sariban E. , Mitchell T. , Kufe D. Expression of the c-Fos proto-oncogene during human monocytic differentiation . Nature 316:64-66, 1985

16.

Kruijer W. , Schubert D. , Verma IM Induction of the proto-oncogene Fos by nerve growth factor. Proc Natl Acad Sci USA 82:7330-7334, 1985

17.

Greenburg ME , Ziff EB Stimulation of 3T3 cells induces transcription of the c-fos proto-oncogene. Nature 311:433-438, 1984

18.

Reiss M. , Stash EB , Velluci VF , Zhou ZL Activation of the autocrine transforming growth factor pathway in human squamous cell carcinoma cells. Cancer Res 51:6254-6262, 1991

19.

Coffey RJ , Derynck R. , Wilcox JN , Brineman TS , Goustin AS , Moses HL , Pittelkow MR Production and autoinduction of transforming growth factor-alpha in human keratinocytes. Nature 328: 817-820, 1987

20.

Vassar R. , Fuchs E. Transgenic mice provide new insights into the role of TGF-alpha during epidermal development and differentiation. Gene Develop 5:714-727, 1991

21.

Murphy LD , Valverius EM , Tsokos M. , Mickley LA , Rosen N. , Bates SE Modulation of EGF receptor expression by differentiating agents in human colon carcinoma cell lines. Cancer Comm 2(10):345-355, 1990

22.

Greenhalgh DA , Welty DJ , Player A. , Yuspa SH Two oncogenes, v-Fos and v-Ras, cooperate to convert normal keratinocytes to squamous cell carcinoma. Proc Natl Acad Sci USA 87:643-647, 1990

23.

Balmain A. , Ramsden M. , Bowden GT , Smith J. Activation of the mouse cellular Harvey-ras gene in chemically induced benign skin papillomas. Nature 307:658-660, 1984

24.

Nelson MA , Futscher BW , Kinsella T. , Wymer J. , Bowden CT Detection of mutant Ha-ras genes in chemically initiated mouse skin epidermis before the development of benign tumors. Proc Natl Acad Sci USA 89:6398-6402, 1992

25.

Brown K. , Buchmann A. , Balmain A. Carcinogen-induced mutations in the mouse c-Ha-ras gene provide evidence of multiple pathways for tumor progression. Proc Natl Acad Sci USA 87:538-542, 1990

26.

Leon J. , Kamino H. , Steinberg JJ , Pellicer A. H-ras activation in benign and self regressing skin tumors (keratoacanthomas) in both humans and an animal model system. Mol Cell Biol 8:786-793, 1988 .