The Bcl‐xL inhibitor of apoptosis is preferentially expressed in cutaneous squamous cell carcinoma compared with that in keratoacanthoma

Keratoacanthoma (KA) is difficult to histologically distinguish from squamous cell carcinoma (SCC). Therefore, although KA is a benign self‐resolving skin lesion, KA is commonly treated as SCC. Biomarkers to distinguish KA and SCC would thus be desirable. In search for specific markers, paraffin‐embedded tissue samples from 25 SCC and 64 KA were arranged in a tissue microarray (TMA) and stained for immunologic cell‐markers CD3, CD20 and CD68 as well as for proteins considered of relevance in tumorgenesis, namely NFκB/p65, IκB‐α, STAT3, p53, TRAP‐1, pRB, phosphorylated pRb, Cyld, p21, p16INK4, Survivin, Bcl‐xL, Caspase 3, Bak, FLK‐1/VEGF‐r2 and Ki‐67. In addition, the tumors were tested for presence of human papillomavirus by PCR. We detected that the two lesions differed significantly in expression of Bcl‐xL which was present in 84% of the SCC compared with only 15% in the KA (p < 0.001). The lower expression of the antiapoptotic protein Bcl‐xL in KA is consistent with a possible role of apoptosis in the regression of KA. © 2008 Wiley‐Liss, Inc.

[1]  Suzanne M Olbricht,et al.  Cutaneous squamous cell carcinoma. , 2008, Advances in dermatology.

[2]  R. Benger,et al.  Lung metastases in a case of metatypical basal cell carcinoma of the eyelid: an illustrative case and literature review to heighten vigilance of its metastatic potential , 2008, Clinical & experimental ophthalmology.

[3]  N. Kiviat,et al.  Detection of human papillomavirus DNA in cutaneous squamous cell carcinoma among immunocompetent individuals. , 2008, The Journal of investigative dermatology.

[4]  M. Feltkamp,et al.  Beta-papillomavirus infection and skin cancer. , 2008, The Journal of investigative dermatology.

[5]  Victor G Prieto,et al.  Metastatic basal cell carcinoma exhibits reduced actin expression , 2008, Modern Pathology.

[6]  D. Ribeiro,et al.  Expression of apoptotic and cell proliferation regulatory proteins in keratoacanthomas and squamous cell carcinomas of the skin. , 2008, Pathology, research and practice.

[7]  O. Forslund Genetic diversity of cutaneous human papillomaviruses. , 2007, The Journal of general virology.

[8]  J. Dillner,et al.  Cutaneous human papillomaviruses found in sun-exposed skin: Beta-papillomavirus species 2 predominates in squamous cell carcinoma. , 2007, The Journal of infectious diseases.

[9]  A. Khachemoune,et al.  Keratoacanthoma: a tumor in search of a classification , 2007, International journal of dermatology.

[10]  J. Dillner,et al.  Characterization of two novel cutaneous human papillomaviruses, HPV93 and HPV96. , 2007, The Journal of general virology.

[11]  O. Larkö,et al.  Human papilloma virus in skin, mouth and uterine cervix in female renal transplant recipients with or without a history of cutaneous squamous cell carcinoma. , 2007, Acta dermato-venereologica.

[12]  T. Batinac,et al.  A comparative study of granzyme B expression in keratoacanthoma and squamous cell carcinoma. , 2006, Journal of dermatological science.

[13]  U. Saarialho-Kere,et al.  Transformation-specific matrix metalloproteinases, MMP-7 and MMP-13, are present in epithelial cells of keratoacanthomas , 2006, Modern Pathology.

[14]  T. Batinac,et al.  Expression of cell cycle and apoptosis regulatory proteins in keratoacanthoma and squamous cell carcinoma. , 2006, Pathology, research and practice.

[15]  B. Akgül,et al.  HPV‐associated skin disease , 2006, The Journal of pathology.

[16]  M. Slater,et al.  Differentiating keratoacanthoma from squamous cell carcinoma by the use of apoptotic and cell adhesion markers , 2005, Histopathology.

[17]  C. Proby,et al.  Human papillomavirus-DNA loads in actinic keratoses exceed those in non-melanoma skin cancers. , 2005, The Journal of investigative dermatology.

[18]  Roy Armstrong,et al.  UV dose determines key characteristics of nonmelanoma skin cancer. , 2004, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[19]  J. Dillner,et al.  High prevalence of cutaneous human papillomavirus DNA on the top of skin tumors but not in "Stripped" biopsies from the same tumors. , 2004, The Journal of investigative dermatology.

[20]  M. Teh,et al.  Biological behavior of keratoacanthoma and squamous cell carcinoma: telomerase activity and COX-2 as potential markers , 2004, Modern Pathology.

[21]  R. Schwartz Keratoacanthoma: A Clinico‐Pathologic Enigma , 2004, Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.].

[22]  Michael Berger,et al.  Apoptosis - the p53 network , 2003, Journal of Cell Science.

[23]  O. Clausen,et al.  Identification of human papillomavirus in keratoacanthomas , 2003, Journal of cutaneous pathology.

[24]  O. Forslund,et al.  Improved detection of cutaneous human papillomavirus DNA by single tube nested 'hanging droplet' PCR. , 2003, Journal of virological methods.

[25]  A. Storey,et al.  Reduced apoptotic levels in squamous but not basal cell carcinomas correlates with detection of cutaneous human papillomavirus , 2002, British Journal of Cancer.

[26]  F. Pontén,et al.  Persistent p53 mutations in single cells from normal human skin. , 2001, The American journal of pathology.

[27]  S. Kondo,et al.  Differences between squamous cell carcinoma and keratoacanthoma in angiotensin type-1 receptor expression. , 2001, The American journal of pathology.

[28]  J. Trapani,et al.  A fresh look at tumor immunosurveillance and immunotherapy , 2001, Nature Immunology.

[29]  B. Hansson,et al.  The Ubiquity and Impressive Genomic Diversity of Human Skin Papillomaviruses Suggest a Commensalic Nature of These Viruses , 2000, Journal of Virology.

[30]  Miranda Thomas,et al.  Role of Bak in UV-induced apoptosis in skin cancer and abrogation by HPV E6 proteins. , 2000, Genes & development.

[31]  N. Kiviat Papillomaviruses in non-melanoma skin cancer: epidemiological aspects. , 1999, Seminars in cancer biology.

[32]  L. Liotta,et al.  A model for CD8+ CTL tumor immunosurveillance and regulation of tumor escape by CD4 T cells through an effect on quality of CTL. , 1999, Journal of immunology.

[33]  R. Stern The mysteries of geographic variability in nonmelanoma skin cancer incidence. , 1999, Archives of dermatology.

[34]  E. Stockfleth,et al.  Identification of DNA Sequences of Both Genital and Cutaneous HPV Types in a Small Number of Keratoacanthomas of Nonimmunosuppressed Patients , 1999, Dermatology.

[35]  J. Kononen,et al.  Tissue microarrays for high-throughput molecular profiling of tumor specimens , 1998, Nature Medicine.

[36]  H. Pfister,et al.  Detection of new human papillomavirus sequences in skin lesions of a renal transplant recipient and characterization of one complete genome related to epidermodysplasia verruciformis-associated types. , 1998, The Journal of general virology.

[37]  O. Olopade,et al.  Overexpression of BCL-x protein in primary breast cancer is associated with high tumor grade and nodal metastases. , 1997, The cancer journal from Scientific American.

[38]  John Calvin Reed,et al.  Elevated expression of Bcl-X and reduced Bak in primary colorectal adenocarcinomas. , 1996, Cancer research.

[39]  John Calvin Reed,et al.  Immunohistochemical analysis of bcl-2, bax, bcl-X, and mcl-1 expression in prostate cancers. , 1996, The American journal of pathology.

[40]  M. Michal,et al.  Patterns of Cell Proliferation in Actinic Keratoacanthomas and Squamous Cell Carcinomas of the Skin: Immunohistochemical Study Using the MIB 1 Antibody in Formalin‐Fixed Paraffin Sections , 1995, The American Journal of dermatopathology.

[41]  Z. Argényi,et al.  Keratoacanthoma Versus Squamous Cell Carcinoma: An Immunohistochemical Reappraisal of p53 Protein and Proliferating Cell Nuclear Antigen Expression in Keratoacanthoma‐Like Tumors , 1995, The American Journal of dermatopathology.

[42]  G. Halliday,et al.  Spontaneous regression of human melanoma/nonmelanoma skin cancer: Association with infiltrating CD4+ T cells , 1995, World Journal of Surgery.

[43]  P. Leboit,et al.  p53 oncoprotein expression and proliferation index in keratoacanthoma and squamous cell carcinoma. , 1994, Archives of dermatology.

[44]  C. Perez Nonmelanoma cancers of the skin. , 1993, The New England journal of medicine.

[45]  P. Kanetsky,et al.  p16 expression in keratoacanthomas and squamous cell carcinomas of the skin: an immunohistochemical study. , 2006, Archives of pathology & laboratory medicine.

[46]  B. Smoller,et al.  VCAM (CD-106) and ICAM (CD-54) Adhesion Molecules Distinguish Keratoacanthomas from Cutaneous Squamous Cell Carcinomas , 2003, Modern Pathology.

[47]  B. Smoller,et al.  The Level of Syndecan-1 Expression is a Distinguishing Feature in Behavior between Keratoacanthoma and Invasive Cutaneous Squamous Cell Carcinoma , 2002, Modern Pathology.

[48]  B. Nickoloff,et al.  Differential expression of cell survival and cell cycle regulatory proteins in cutaneous squamoproliferative lesions. , 1999, Journal of dermatological science.

[49]  M. Manos,et al.  19 – SAMPLE PREPARATION FROM PARAFFIN-EMBEDDED TISSUES , 1990 .