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

Year 2023, Volume: 30 Issue: 2, 193 - 202, 22.06.2023

Afife Uğuz , Nermin Karahan

https://doi.org/10.17343/sdutfd.1268022

Abstract

Amaç
Amaç: İnvaziv melanomun (İM) en önemli prognostik
faktörleri patolojik evreleme ve metastaz varlığı olarak
bilinmektedir. Patolojik evrelemede tümör boyutu, invazyon
derinliği, ülserasyon, mitotik indeks önem arz
etmektedir. Çalışmamızda BRAF V600E ve CD271’in
immünohistokimyasal (İHK) ekspresyonları ile klinikopatolojik
parametreler ve prognoz ile ilişkisinin incelenmesi
amaçlanmıştır.
Gereç ve Yöntem
Çalışmamızda Süleyman Demirel Üniversitesi Patoloji
Anabilim Dalı’nda Aralık 2010 - Mayıs 2017 tarihleri
arasında tanı almış 47 İM olgusu incelendi. Bu olgulara
BRAF V600E ve CD271 belirleyicileri uygulandı. Bu
belirteçlerin primer ve metastatik İM’lerda ve sağkalım
ile ilişkisi immünohistokimyasal yöntemle araştırıldı.
Ayrıca primer ve metastatik İM’ların ülser, lenfositik infiltrasyon,
pigmentasyon, mitoz, Breslow kalınlığı, metastaz
yapıp yapmaması, yaş, cinsiyet ve sağkalım ile
ilişkisi araştırıldı.
Bulgular
Primer İM’ler ve metastatik İM’ler karşılaştırıldığında
ülserasyon, mitotik indeks açısından, aralarındaki fark
istatistiksel olarak anlamlı bulunurken, Breslow tümör
kalınlığı, lenfositik infiltrasyon, pigmentasyon, CD271
ve BRAF V600E ekspresyonu açısından aralarındaki
fark istatistiksel olarak anlamlı bulunmadı. Sağkalım
ile ilişkilerine bakıldığında Breslow tümör kalınlığı, ülserasyon,
BRAF V600E ekspresyonu şiddeti, BRAF
V600E ekspresyonu olmayanlar ile olanlar arasındaki
ve BRAF V600E ekspresyon şiddeti 3+ olanlar ile
diğerleri arasındaki fark istatistiksel olarak anlamlı
bulundu. Cinsiyet, pigmentasyon, BRAF V600E ekspresyon
yüzdesi, CD271 ekspresyon şiddeti, CD271
ekspresyon yüzdesi ile sağkalım arasında istatistiksel
olarak anlamlı fark bulunmadı. Çalışmamızda Primer
İM’si olan bireylerin yaşları 35-93 arasında değişmekte
olup ortalama 64,12 ± 20,35, metastatik İM grubundaki
bireylerin yaşları 35-89 arasında değişmekte olup ortalama
69 ± 13,42 idi. Yaş yönünden iki grup arasındaki
fark anlamlı bulunmadı.
Sonuç
Çalışmamız sonucunda elde ettiğimiz verilerde BRAF
V600E ekspresyonu prognoz ile ilişkili olduğu gözükmektedir.
BRAF V600E ekspresyonu olmayanlarda
yüksek sağkalım oranları varken ekspresyon şiddeti
yüksek olanlarda sağkalımın azaldığı bulundu. Çalışmamızda
CD271 ekspresyon şiddeti ve yüzdesi açısından
primer ve metastatik İM gruplarında ve sağkalım
arasında istatistiksel olarak anlamlı fark bulmadık.

Keywords

BRAF, CD271, immünohistokimya, prognostik faktörler, İnvaziv melanom

Supporting Institution

üleyman Demirel Üniversitesi Bilimsel Araştırma Proje Koordinasyon Birimi

Project Number

4811-TU1-16

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

Abstract

Objective
Metastasis and pathological staging are considered the
primary prognostic indicators for invasive melanoma
(IM). Pathological staging is determined by evaluating
tumor size, depth of invasion, ulceration, and mitotic
index. Our study aims to explore the relationship
between the prognosis of BRAF V600E and CD271
and their immunohistochemical expressions, as well
as clinicopathological parameters.
Materials and Methods
Our study analyzed 47 cases of IM that were observed
between December 2010 and May 2017 at Süleyman
Demirel University's Department of Pathology. These
cases were assessed using BRAF V600E and
CD271 markers, and their correlation with primary
and metastatic IM, as well as survival rates, were
examined using immunohistochemical analysis. We
also investigated the relationship between referral,
lymphocytic infiltration, pigmentation, mitosis, Breslow
depth, lack of metastasis screening, age, gender, and
survival to provide a comprehensive understanding of
the factors that may influence the disease progression
and patient outcomes.
Results
The age of the primary IM patients ranged from 35 to
93 years old, with an average of 64.12 ± 20.35 years.
The age of the metastatic IM patients ranged from 35
to 89 years old, with an average of 69 ± 13.42 years.
Our analysis did not reveal any statistically significant
differences in age between these two groups. Significant
statistical differences were observed between primary
IM and metastatic IM in terms of ulceration and mitotic
index. However, there were no significant differences
between these two groups in Breslow tumor thickness,
lymphocytic infiltration, pigmentation, or the expression
of CD271 and V600E. In terms of survival, statistically
significant differences were observed in relation to
Breslow tumor thickness, ulceration, and the intensity
of BRAF V600E expression, as well as between
individuals with and without expression of BRAF
V600E, specifically in cases with a 3+ expression
intensity. No significant differences were observed
in relation to gender, pigmentation, BRAF V600E
percentage of expression, CD271 expression intensity,
or survival. We did not determine a statistically
significant difference between primary and metastatic
IM groups and survival in terms of CD271 expression
severity and percentage in our study.
Conclusion
In summary, our findings suggest that the expression
of BRAF V600E is associated with prognosis, with
patients without this expression exhibiting a higher
survival rate. However, our results indicate that the
survival rate decreases as the intensity of expression
increases.

Keywords

BRAF, CD271, immunohistochemistry, prognostic factors, invasive melanoma

Project Number

4811-TU1-16

References

• 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.