Melanositik lezyonlarda p16 ve CD117 ekspresyonunun önemi
Yıl 2021,
, 113 - 119, 30.08.2021
Sevil Karabağ
,
Ayşegül İsal Arslan
Öz
Amaç: Bu çalışmada melanositik lezyonların p16 ve CD117 ekspresyon profillerini belirleyerek, melanomun diğer benign ya da potansiyel prekürsör melanositik lezyonlardan ayırıcı tanısını yapmayı kolaylaştıracak immün profillerini saptamayı amaçladık.
Gereç ve Yöntem: Seksen bir melanositik lezyon olgusuna immünohistokimya ile p16 ve CD117 uygulandı.
Bulgular: Melanom olgularında diğer benign ve prekürsör melanositik lezyonlara kıyasla anlamlı olarak p16 ekpresyon kaybı mevcuttur(p<0.05). Ayrıca displastik nevüs olgularında da intradermal nevüs olgularına göre anlamlı olarak p16 ekspresyonunda kayıp mevcuttur (p<0.01). CD117 ise intradermal nevüslerde eksprese olmaz iken, spitz nevüs, blue nevüs, invaziv melanom ve displastik nevüslerde ise yüksek oranda ekspresyon mevcuttur (p<0.01).
Sonuç: p16 ve CD117 belirteçlerinin birlikte kullanıldığı zaman, melanomları benign lezyonlardan ve benign lezyonları potansiyel prekürsör melanositik lezyonlardan ayırımda önemli belirteçler olarak katkı sağlayacağını düşünmekteyiz.
Destekleyen Kurum
Araştırmanın destekleyicisi bulunmamaktadır
Kaynakça
- Fouchardiere A, Caillot C, Jacquemus J, et al. β-Catenin nuclear expression discriminates deep penetrating nevi from other cutaneous melanocytic tumors. Virchows Archiv 2019; 474:539–550
- Whittaker S. Adjuvant diagnosis of malignant melanoma. Clin Exp Dermatol. 2000; 25(6):497–502.
- Koh SS, Cassarino DS. Immunohistochemical Expression of p16 in Melanocytic Lesions An Updated Review and Meta-analysis. Arch Pathol Lab Med 2018; 142, July
Troxel DB. Medicolegal aspects of error in pathology. Arch Pathol Lab Med. 2006;130(5):617–619
- Ferringer T. Immunohistochemistry in Dermatopathology. Arch Pathol Lab Med 2015; Vol 139, January
- Chandler H, Peters G. Stressing the cell cycle in senescence and aging. Curr Opin Cell Biol. 2013;25(6):765-771.
- Ha L, Merlino G, Sviderskaya EV. Melanomagenesis: overcoming the barrier of melanocyte senescence. Cell Cycle. 2008;7(13):1944–1948.
- Fung C, Pupo GM, Scolyer RA. P16 (INK)(4a) deficiency promotes DNA hyper-replication and genetic instability in melanocytes. Pigment Cell Melanoma Res. 2014;26(2):236–246.
- Hussussian CJ, Struewing JP, Goldstein AM, et al. Germline p16 mutations in familial melanoma. Nat Genet. 1994; 8(1):15-21
- Charpin C, Giusiano S, Charfi S, et al. Quantitative immunohistochemical expression of c Kit in breast carcinomas is predictive of patients’ outcome. Br J Cancer. 2009;101:48–54.
- Lin YC, Chang YM, Ho JY, et al. C-kit Expression of Melanocytic Neoplasm and Association With Clinicopathological Parameters and Anatomic Locations in Chinese People. Am J Dermatopathol 2013;35:569–575
- Went PT, Dirnhofer S, Bundi M, et al. Prevalence of KIT expression in human tumors. J Clin Oncol 2004; 22: 4514–4522.
- Willmore-Payne C, Layfield LJ, Holden JA. C-KIT mutation analysis for diagnosis of gastrointestinal stromal tumors in fine needle aspiration specimens. Cancer 2005; 105: 165–170.
- Koh SS, Roehmholdt BF, Cassarino DS. Immunohistochemistry of p16 in nevi of pregnancy and nevoid melanomas. J Cutan Pathol. 2018; 45:891–896.
- Liu HG, Kong MX, Yao Q, et al. Expression of Sox10 and c-kit in Sinonasal Mucosal Melanomas Arising in the Chinese Population. Head and Neck Pathol 2012; 6:401–408.
- Elder DE, Massi D, Scolyer R, Willemze R. WHO classification of skin tumours. 4th ed. IARC Press, Lyon; 2018
- Costa S, Byrne M, Pissaloux D, et al. Melanomas associated with blue nevi or mimicking cellular blue nevi: clinical, pathologic, and molecular study of 11 cases displaying a high frequency of GNA11 mutations, BAP1 expression loss, and a predilection for the scalp. Am J Surg Pathol 2016; 40:368–377.
- Antonescu CR, Busam KJ, Francone TD, et al. L567P KIT mutation in anal melanomas correlates with KIT protein expression and is sensitive to specific kinase inhibition. Int J Cancer. 2007;121:257–64.
- Beadling C, Jacobson-Dunlop E, Hodi FS, et al. KIT gene mutations and copy number in melanoma subtypes. Clin Cancer Res. 2008;14:6821–8.
- Satzger I, Schaefer T, Kuettler U, et al. Analysis of c-KIT expression and KIT gene mutation in human mucosal melanomas. Br J Cancer. 2008;99:2065–9.
- Torres-Cabala CA, Wang WL, Trent J, et al. Correlation between KIT expression and KIT mutation in melanoma: a study of 173 cases with emphasis on the acral-lentiginous/mucosal type. Mod Pathol. 2009;22:1446–56.
- Curtin JA, Busam K, Pinkel D, Bastian BC. Somatic activation of KIT in distinct subtypes of melanoma. J Clin Oncol. 2006;24:4340–6.
- Alexis BJ, Martinez AE, Lutzky J. An immunohistochemical evaluation of c-kit (CD117) expression in malignant melanoma, and results of imatinib mesylate (Gleevec) therapy in three patients. Melanoma Res. 2005;15:283–5.
- Pilloni L, Bianco P, Difelice E, et al. The usefulness of c-Kit in the immunohistochemical assessment of melanocytic lesions. European Journal of Histochemistry 2011; 55: 20.
- Meng D, Carvajal RD. KIT as an Oncogenic Driver in Melanoma: An Update on Clinical Development. American Journal of Clinical Dermatology 2019; 20:315–323.
- Sa BC, Fugimori ML, Ribeiro KC, et al. Proteins involved in pRb and p53 pathways are differentially expressed in thin and thick superficial spreading melanomas. Melanoma Res. 2009; 19(3):135-141.
- Demirkan NC, Kesen Z, Akdag B, Delmas V. The effect of the sun on expression of beta-catenin, p16 and cyclin d1 proteins in melanocytic lesions. Clin Exp Dermatol. 2007; 32(6):733–739.
- Zoroquiain P, Fernandes BF, Gonzalez S, Novais GN, Schalper KA, Burnier MN. p16ink4a expression in benign and malignant melanocytic conjunctival lesions. Int J Surg Pathol. 2012; 20(3):240–245.
- Reed JA, Loganzo F, Shea CR, et al. Loss of expression of the p16/cyclindependent kinase inhibitor 2 tumor suppressor gene in melanocytic lesions correlates with invasive stage of tumor progression. Cancer Res. 1995; 55(13):2713–2718.
- Tran SL, Haferkamp S, Scurr LL, et al. Absence of distinguishing senescence traits in human melanocytic nevi. J Invest Dermatol. 2012; 132(9):2226–2234.
- Mihic-Probst D, Saremaslani P, Komminoth P, Heitz PU. Immunostaining for the tumour suppressor gene p16 product is a useful marker to differentiate melanoma metastasis from lymph-node nevus. Virchows Arch. 2003;443(6):745–751.
- Piana S, Tagliavini E, Ragazzi M, et al. Lymph node melanocytic nevi: pathogenesis and differential diagnoses, with special reference to p16 reactivity. Pathol Res Pract. 2015;211(5):381–388.
The importance of p16 and CD117 expression in melanocytic lesions
Yıl 2021,
, 113 - 119, 30.08.2021
Sevil Karabağ
,
Ayşegül İsal Arslan
Öz
Aim: The present study aims to determine the p16 and CD117 expression profiles of melanocytic lesions to investigate immune profiles that may facilitate differential diagnosis of melanoma from benign or potential precursor melanocytic lesions.
Materials and Methods: Immunohistochemistry for p16 and CD117 was applied in a total of 81 cases with melanocytic lesions.
Results: A significant loss of p16 expression was found in melanoma cases compared to benign and precursor melanocytic lesions (p<0.05). Moreover, a significant loss of p16 expression was also noted in cases of dysplastic nevus compared to those with intradermal nevus (p<0.01). While no CD117 expression was observed in intradermal nevi, high-level expression was seen in cases with Spitz nevus, blue nevus, invasive melanoma and dysplastic nevus (p<0.01).
Conclusion: We believe using p16 and CD117 together may provide an important marker combination to aid in distinguishing melanoma from benign lesions and benign lesions from potential precursor melanocytic lesions.
Kaynakça
- Fouchardiere A, Caillot C, Jacquemus J, et al. β-Catenin nuclear expression discriminates deep penetrating nevi from other cutaneous melanocytic tumors. Virchows Archiv 2019; 474:539–550
- Whittaker S. Adjuvant diagnosis of malignant melanoma. Clin Exp Dermatol. 2000; 25(6):497–502.
- Koh SS, Cassarino DS. Immunohistochemical Expression of p16 in Melanocytic Lesions An Updated Review and Meta-analysis. Arch Pathol Lab Med 2018; 142, July
Troxel DB. Medicolegal aspects of error in pathology. Arch Pathol Lab Med. 2006;130(5):617–619
- Ferringer T. Immunohistochemistry in Dermatopathology. Arch Pathol Lab Med 2015; Vol 139, January
- Chandler H, Peters G. Stressing the cell cycle in senescence and aging. Curr Opin Cell Biol. 2013;25(6):765-771.
- Ha L, Merlino G, Sviderskaya EV. Melanomagenesis: overcoming the barrier of melanocyte senescence. Cell Cycle. 2008;7(13):1944–1948.
- Fung C, Pupo GM, Scolyer RA. P16 (INK)(4a) deficiency promotes DNA hyper-replication and genetic instability in melanocytes. Pigment Cell Melanoma Res. 2014;26(2):236–246.
- Hussussian CJ, Struewing JP, Goldstein AM, et al. Germline p16 mutations in familial melanoma. Nat Genet. 1994; 8(1):15-21
- Charpin C, Giusiano S, Charfi S, et al. Quantitative immunohistochemical expression of c Kit in breast carcinomas is predictive of patients’ outcome. Br J Cancer. 2009;101:48–54.
- Lin YC, Chang YM, Ho JY, et al. C-kit Expression of Melanocytic Neoplasm and Association With Clinicopathological Parameters and Anatomic Locations in Chinese People. Am J Dermatopathol 2013;35:569–575
- Went PT, Dirnhofer S, Bundi M, et al. Prevalence of KIT expression in human tumors. J Clin Oncol 2004; 22: 4514–4522.
- Willmore-Payne C, Layfield LJ, Holden JA. C-KIT mutation analysis for diagnosis of gastrointestinal stromal tumors in fine needle aspiration specimens. Cancer 2005; 105: 165–170.
- Koh SS, Roehmholdt BF, Cassarino DS. Immunohistochemistry of p16 in nevi of pregnancy and nevoid melanomas. J Cutan Pathol. 2018; 45:891–896.
- Liu HG, Kong MX, Yao Q, et al. Expression of Sox10 and c-kit in Sinonasal Mucosal Melanomas Arising in the Chinese Population. Head and Neck Pathol 2012; 6:401–408.
- Elder DE, Massi D, Scolyer R, Willemze R. WHO classification of skin tumours. 4th ed. IARC Press, Lyon; 2018
- Costa S, Byrne M, Pissaloux D, et al. Melanomas associated with blue nevi or mimicking cellular blue nevi: clinical, pathologic, and molecular study of 11 cases displaying a high frequency of GNA11 mutations, BAP1 expression loss, and a predilection for the scalp. Am J Surg Pathol 2016; 40:368–377.
- Antonescu CR, Busam KJ, Francone TD, et al. L567P KIT mutation in anal melanomas correlates with KIT protein expression and is sensitive to specific kinase inhibition. Int J Cancer. 2007;121:257–64.
- Beadling C, Jacobson-Dunlop E, Hodi FS, et al. KIT gene mutations and copy number in melanoma subtypes. Clin Cancer Res. 2008;14:6821–8.
- Satzger I, Schaefer T, Kuettler U, et al. Analysis of c-KIT expression and KIT gene mutation in human mucosal melanomas. Br J Cancer. 2008;99:2065–9.
- Torres-Cabala CA, Wang WL, Trent J, et al. Correlation between KIT expression and KIT mutation in melanoma: a study of 173 cases with emphasis on the acral-lentiginous/mucosal type. Mod Pathol. 2009;22:1446–56.
- Curtin JA, Busam K, Pinkel D, Bastian BC. Somatic activation of KIT in distinct subtypes of melanoma. J Clin Oncol. 2006;24:4340–6.
- Alexis BJ, Martinez AE, Lutzky J. An immunohistochemical evaluation of c-kit (CD117) expression in malignant melanoma, and results of imatinib mesylate (Gleevec) therapy in three patients. Melanoma Res. 2005;15:283–5.
- Pilloni L, Bianco P, Difelice E, et al. The usefulness of c-Kit in the immunohistochemical assessment of melanocytic lesions. European Journal of Histochemistry 2011; 55: 20.
- Meng D, Carvajal RD. KIT as an Oncogenic Driver in Melanoma: An Update on Clinical Development. American Journal of Clinical Dermatology 2019; 20:315–323.
- Sa BC, Fugimori ML, Ribeiro KC, et al. Proteins involved in pRb and p53 pathways are differentially expressed in thin and thick superficial spreading melanomas. Melanoma Res. 2009; 19(3):135-141.
- Demirkan NC, Kesen Z, Akdag B, Delmas V. The effect of the sun on expression of beta-catenin, p16 and cyclin d1 proteins in melanocytic lesions. Clin Exp Dermatol. 2007; 32(6):733–739.
- Zoroquiain P, Fernandes BF, Gonzalez S, Novais GN, Schalper KA, Burnier MN. p16ink4a expression in benign and malignant melanocytic conjunctival lesions. Int J Surg Pathol. 2012; 20(3):240–245.
- Reed JA, Loganzo F, Shea CR, et al. Loss of expression of the p16/cyclindependent kinase inhibitor 2 tumor suppressor gene in melanocytic lesions correlates with invasive stage of tumor progression. Cancer Res. 1995; 55(13):2713–2718.
- Tran SL, Haferkamp S, Scurr LL, et al. Absence of distinguishing senescence traits in human melanocytic nevi. J Invest Dermatol. 2012; 132(9):2226–2234.
- Mihic-Probst D, Saremaslani P, Komminoth P, Heitz PU. Immunostaining for the tumour suppressor gene p16 product is a useful marker to differentiate melanoma metastasis from lymph-node nevus. Virchows Arch. 2003;443(6):745–751.
- Piana S, Tagliavini E, Ragazzi M, et al. Lymph node melanocytic nevi: pathogenesis and differential diagnoses, with special reference to p16 reactivity. Pathol Res Pract. 2015;211(5):381–388.