sdü tıp fak derg

Medical Journal of Süleyman Demirel University

2602-2109

Süleyman Demirel Üniversitesi

10.17343/sdutfd.1268022

Clinical Sciences

Klinik Tıp Bilimleri

INVESTIGATION OF THE RELATIONSHIP BETWEEN CD271 AND BRAF EXPRESSION WITH CLINICOPATHOLOGICAL PARAMETERS BY IMMUNOHISTOCHEMICAL METHOD IN INVASIVE MELANOMA

İNVAZİV MELANOMLARDA CD271 VE BRAF EKSPRESYONUNUN KLİNİKOPATOLOJİK PARAMETRELERLE VE PROGNOZ İLE İLİŞKİSİNİN İMMÜNOHİSTOKİMYASAL YÖNTEMLE ARAŞTIRILMASI

https://orcid.org/0000-0002-3886-5099

Uğuz

Afife

https://orcid.org/0000-0003-0883-4037

Karahan

Nermin

SULEYMAN DEMIREL UNIVERSITY

06 22 2023

30 2 193 202 03 20 2023 04 09 2023

1994

Süleyman Demirel Üniversitesi Tıp Fakültesi Dergisi

ObjectiveMetastasis and pathological staging are considered theprimary prognostic indicators for invasive melanoma(IM). Pathological staging is determined by evaluatingtumor size, depth of invasion, ulceration, and mitoticindex. Our study aims to explore the relationshipbetween the prognosis of BRAF V600E and CD271and their immunohistochemical expressions, as wellas clinicopathological parameters.Materials and MethodsOur study analyzed 47 cases of IM that were observedbetween December 2010 and May 2017 at SüleymanDemirel University's Department of Pathology. Thesecases were assessed using BRAF V600E andCD271 markers, and their correlation with primaryand metastatic IM, as well as survival rates, wereexamined using immunohistochemical analysis. Wealso investigated the relationship between referral,lymphocytic infiltration, pigmentation, mitosis, Breslowdepth, lack of metastasis screening, age, gender, andsurvival to provide a comprehensive understanding ofthe factors that may influence the disease progressionand patient outcomes.ResultsThe age of the primary IM patients ranged from 35 to93 years old, with an average of 64.12 ± 20.35 years.The age of the metastatic IM patients ranged from 35to 89 years old, with an average of 69 ± 13.42 years.Our analysis did not reveal any statistically significantdifferences in age between these two groups. Significantstatistical differences were observed between primaryIM and metastatic IM in terms of ulceration and mitoticindex. However, there were no significant differencesbetween these two groups in Breslow tumor thickness,lymphocytic infiltration, pigmentation, or the expressionof CD271 and V600E. In terms of survival, statisticallysignificant differences were observed in relation toBreslow tumor thickness, ulceration, and the intensityof BRAF V600E expression, as well as betweenindividuals with and without expression of BRAFV600E, specifically in cases with a 3+ expressionintensity. No significant differences were observedin relation to gender, pigmentation, BRAF V600Epercentage of expression, CD271 expression intensity,or survival. We did not determine a statisticallysignificant difference between primary and metastaticIM groups and survival in terms of CD271 expressionseverity and percentage in our study.ConclusionIn summary, our findings suggest that the expressionof BRAF V600E is associated with prognosis, withpatients without this expression exhibiting a highersurvival rate. However, our results indicate that thesurvival rate decreases as the intensity of expressionincreases.

AmaçAmaç: İnvaziv melanomun (İM) en önemli prognostikfaktörleri patolojik evreleme ve metastaz varlığı olarakbilinmektedir. Patolojik evrelemede tümör boyutu, invazyonderinliği, ülserasyon, mitotik indeks önem arzetmektedir. Çalışmamızda BRAF V600E ve CD271’inimmünohistokimyasal (İHK) ekspresyonları ile klinikopatolojikparametreler ve prognoz ile ilişkisinin incelenmesiamaçlanmıştır.Gereç ve YöntemÇalışmamızda Süleyman Demirel Üniversitesi PatolojiAnabilim Dalı’nda Aralık 2010 - Mayıs 2017 tarihleriarasında tanı almış 47 İM olgusu incelendi. Bu olgularaBRAF V600E ve CD271 belirleyicileri uygulandı. Bubelirteçlerin primer ve metastatik İM’lerda ve sağkalımile ilişkisi immünohistokimyasal yöntemle araştırıldı.Ayrıca primer ve metastatik İM’ların ülser, lenfositik infiltrasyon,pigmentasyon, mitoz, Breslow kalınlığı, metastazyapıp yapmaması, yaş, cinsiyet ve sağkalım ileilişkisi araştırıldı.BulgularPrimer İM’ler ve metastatik İM’ler karşılaştırıldığındaülserasyon, mitotik indeks açısından, aralarındaki farkistatistiksel olarak anlamlı bulunurken, Breslow tümörkalınlığı, lenfositik infiltrasyon, pigmentasyon, CD271ve BRAF V600E ekspresyonu açısından aralarındakifark istatistiksel olarak anlamlı bulunmadı. Sağkalımile ilişkilerine bakıldığında Breslow tümör kalınlığı, ülserasyon,BRAF V600E ekspresyonu şiddeti, BRAFV600E ekspresyonu olmayanlar ile olanlar arasındakive BRAF V600E ekspresyon şiddeti 3+ olanlar ilediğerleri arasındaki fark istatistiksel olarak anlamlıbulundu. Cinsiyet, pigmentasyon, BRAF V600E ekspresyonyüzdesi, CD271 ekspresyon şiddeti, CD271ekspresyon yüzdesi ile sağkalım arasında istatistikselolarak anlamlı fark bulunmadı. Çalışmamızda PrimerİM’si olan bireylerin yaşları 35-93 arasında değişmekteolup ortalama 64,12 ± 20,35, metastatik İM grubundakibireylerin yaşları 35-89 arasında değişmekte olup ortalama69 ± 13,42 idi. Yaş yönünden iki grup arasındakifark anlamlı bulunmadı.SonuçÇalışmamız sonucunda elde ettiğimiz verilerde BRAFV600E ekspresyonu prognoz ile ilişkili olduğu gözükmektedir.BRAF V600E ekspresyonu olmayanlardayüksek sağkalım oranları varken ekspresyon şiddetiyüksek olanlarda sağkalımın azaldığı bulundu. ÇalışmamızdaCD271 ekspresyon şiddeti ve yüzdesi açısındanprimer ve metastatik İM gruplarında ve sağkalımarasında istatistiksel olarak anlamlı fark bulmadık.

BRAF CD271 immünohistokimya prognostik faktörler İnvaziv melanom

BRAF CD271 immunohistochemistry prognostic factors invasive melanoma

üleyman Demirel Üniversitesi Bilimsel Araştırma Proje Koordinasyon Birimi

4811-TU1-16

1. Guo R, Fierro-Fine A, Goddard L, Russell M, Chen J, Liu CZ, et al. Increased expression of melanoma stem cell marker CD271 in metastatic melanoma to the brain. Int J Clin Exp Pathol. 2014;7(12):8947-51.

2. Schadendorf D, Fisher DE, Garbe C, Gershenwald JE, Grob J-J, Halpern A, et al. Melanoma. J Nat Rev Dis Primers. 2015;1(1):1-20.

3. Eggermont AM, Spatz A, Robert C. Cutaneous melanoma. Lancet. 2014;383(9919):816-27.

4. Akbani R, Akdemir KC, Aksoy BA, Albert M, Ally A, Amin SB, et al. Genomic classification of cutaneous melanoma. J Cell. 2015;161(7):1681-96.

5. Cooper C, Sorrell J, Gerami P. Update in molecular diagnostics in melanocytic neoplasms. Adv Anat Pathol. 2012;19(6):410-6.

6. Rutkowski P, Gos A, Jurkowska M, Switaj T, Dziewirski W, Zdzienicki M, et al. Molecular alterations in clinical stage III cutaneous melanoma: Correlation with clinicopathological features and patient outcome. Oncol Lett. 2014;8(1):47-54.

7. Long GV, Menzies AM, Nagrial AM, Haydu LE, Hamilton AL, Mann GJ, et al. Prognostic and clinicopathologic associations of oncogenic BRAF in metastatic melanoma. J Clin Oncol. 2011;29(10):1239-46.

8. Mar VJ, Liu W, Devitt B, Wong SQ, Dobrovic A, McArthur GA, et al. The role of BRAF mutations in primary melanoma growth rate and survival. Br J Dermatol. 2015;173(1):76-82.

9. Mohamed A, Gonzalez RS, Lawson D, Wang J, Cohen C. Tumor stem cells (CD271, c-kit, SOX10) in Melanomas: prognostic and outcome implications. Appl Immunohistochem Mol Morphol. 2014;22(2):142-5.

10. Beretti F, Manni P, Longo C, Argenziano G, Farnetani F, Cesinaro A, et al. CD271 is expressed in melanomas with more aggressive behaviour, with correlation of characteristic morphology by in vivo reflectance confocal microscopy. J British Journal of Dermatology. 2015;172(3):662-8.

11. Marconi A, Borroni RG, Truzzi F, Longo C, Pistoni F, Pellacani G, et al. Hypoxia‐Inducible Factor‐1α and CD 271 inversely correlate with melanoma invasiveness. J Experimental Dermatology. 2015;24(5):396-8.

12. Sigal AC, Keenan M, Lazova R. P75 nerve growth factor receptor as a useful marker to distinguish spindle cell melanoma from other spindle cell neoplasms of sun-damaged skin. J The American Journal of dermatopathology. 2012;34(2):145-50.

13. Hugdahl E, Kalvenes MB, Puntervoll HE, Ladstein RG, Akslen LA. BRAF-V600E expression in primary nodular melanoma is associated with aggressive tumour features and reduced survival. J British journal of cancer. 2016;114(7):801-8.

14. Lazova R, Tantcheva-Poor I, Sigal AC. P75 nerve growth factor receptor staining is superior to S100 in identifying spindle cell and desmoplastic melanoma. J Journal of the American Academy of Dermatology. 2010;63(5):852-8.

15. Shenenberger DW. Cutaneous malignant melanoma: a primary care perspective. Am Fam Physician. 2012;85(2):161-8.

16. Evans RD, Kopf AW, Lew RA, Rigel DS, Bart RS, Friedman RJ, et al. Risk factors for the development of malignant melanoma—I: Review of case‐control studies. J The Journal of dermatologic surgery. 1988;14(4):393-408.

17. Bartlett EK, Karakousis GC. Current staging and prognostic factors in melanoma. Surg Oncol Clin N Am. 2015;24(2):215-27.

18. Bhandaru M, Ardekani GS, Zhang G, Martinka M, McElwee KJ, Li G, et al. A combination of p300 and Braf expression in the diagnosis and prognosis of melanoma. BMC Cancer. 2014;14(1):398.

19. Chen G, Dudley J, Tseng LH, Smith K, Gurda GT, Gocke CD, et al. Lymph node metastases of melanoma: challenges for BRAF mutation detection. Hum Pathol. 2015;46(1):113-9.

20. Shinozaki M, Fujimoto A, Morton DL, Hoon DS. Incidence of BRAF oncogene mutation and clinical relevance for primary cutaneous melanomas. Clin Cancer Res. 2004;10(5):1753-7.

21. Eigentler T, Assi Z, Hassel JC, Heinzerling L, Starz H, Berneburg M, et al. Which melanoma patient carries a BRAF-mutation? A comparison of predictive models. J Oncotarget. 2016;7(24):36130.

22. Larsen TE, Grude TH. A Retrospective Histological Study of 669 Cases of Primary Cutaneous Malignant Melanoma in Clinical Stage I: 3. The Relation between the Tumour‐Associated Lymphocyte Infiltration and Age and Sex, Tumour Cell Type, Pigmentation, Cellular Atypia, Mitotic Count, Depth of Invasion, Ulceration, Tumour Type and Prognosis. J Acta Pathologica Microbiologica Scandinavica Section A Pathology. 1978;86(1‐6):523-30.

23. Chan MM, Tahan SR. Low‐affinity nerve growth factor receptor (P75 NGFR) as a marker of perineural invasion in malignant melanomas. J Journal of cutaneous pathology. 2010;37(3):336-43.

24. Kumar R, Angelini S, Czene K, Sauroja I, Hahka-Kemppinen M, Pyrhonen S, et al. BRAF mutations in metastatic melanoma: a possible association with clinical outcome. Clin Cancer Res. 2003;9(9):3362-8.

25. Gambichler T, Petig AL, Stockfleth E, Stucker M. Expression of SOX10, ABCB5 and CD271 in melanocytic lesions and correlation with survival data of patients with melanoma. Clin Exp Dermatol. 2016;41(7):709-16.

26. Balch CM, Gershenwald JE, Soong SJ, Thompson JF, Atkins MB, Byrd DR, et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol. 2009;27(36):6199-206.