Immunohistochemical panel assay, including DNA mismatch repair proteins, in Korean actinic keratosis, keratoacanthoma, and squamous cell carcinoma patients

Abstract

Background: Actinic keratoses (AKs) are the most frequently occurring precancerous lesions. Although AKs and squamous cell carcinoma (SCC) in situ have similar genetic profiles, not all AKs progress to SCC, and some AKs regress. Keratoacanthoma (KA) is a relatively common low-grade tumor, and strong arguments confirm the classification of KA as a variant of invasive SCC. However, no single prior study has conducted broad immunohistochemistry (IHC) panels of AK, KA, and SCC samples. Objective: This study was designed to examine the results of IHC panels, including mismatch repair (MMR) gene proteins, in tissue microarrays of AKs, SCCs, KAs, and control non-cancerous skin tissue. Methods: A total of 73 SCC in situ, 77 SCC, 19 KA, 145 AK, and 18 non-cancerous control skin samples were retrospectively retrieved. IHC was performed to detect CD44, S-100, epidermal growth factor receptor (EGFR), pan-cytokeratin (pan-CK), p53, 5-hydroxymethylcytosine (5-hmc), Ki-67, and MMR gene proteins (PMS2, MLH1, MSH2, and MSH6). IHC staining was scored to measure expression levels. Results: Similar CD44-positive tumor cell expression was found in AK, SCC, KA, and SCC in situ (p>0.05). EGFR was most highly expressed in AKs, followed by SCC and SCC in situ (p<0.05). Ki-67 score was highest in SCC in situ (p<0.05), and KA and SCC had higher p53 expression than AK (p<0.05). The lowest expression of PMS2 was in AK, and the lowest expression of MLH1 was in KA (p<0.05). MSH2 and MSH6 showed the highest expression in SCC and SCC in situ (p<0.05). Conclusions: The various IHC profiles of AK, KA, SCC in situ, and SCC, particularly the differences between non-melanoma skin cancers and AKs, can help diagnose patients whose lesions are difficult to differentiate and be helpful in researching new treatments. |저자는 한양대학교병원 피부과에서 편평세포암, 제자리 편평세포암, 각질가시세포종을 포함한 비흑색종 피부암과 암의 전구 병변인 광선각화증으로 진단된 환자들을 대상으로 하여 그룹들 간의 CD44, EGFR, Ki67, S-100, p53, 5-hmc, PMS2, MLH1, MSH2, MSH6의 조직 표본에서의 발현 정도에 관한 비교 분석을 시행하였다. 1. 총 332명의 환자 및 대조군을 대상으로 하였고 (제자리 편평세포암 73명, 편평세포암 77명, 각질가시세포종 19명, 광선각화증 145명, 대조군 18명), CD44, pan-CK, 5-hmc 에 대하여 각질가시세포종, 광선각화증, 편평세포암은 모두 비슷한 발현을 보였다 (p >0.05). 2. EGFR 에 대하여 각질가시세포종과 대조군에서의 발현이 가장 낮게 나타났으며, 광선각화증에서 가장 높은 발현을 보였다 (p <0.05). 3. S-100의 발현은 대조군에서 가장 높았다 (p <0.05). 4. p53의 발현은 각질가시세포종, 각질세포암종군-편평세포암, 제자리 편평세포암-, 광선각화증, 대조군 순이었다 (p <0.05). 5. PMS2의 발현은 광선각화증에서 가장 낮았다 (p <0.05). 6. MLH1의 발현은 각질가시세포종에서 가장 낮았다 (p <0.05). 7. MSH2, MSH6의 발현은 각질세포암종군에서 가장 높게 나타났다 (p<0.05). 결론적으로 본 연구는 각기 다른 면역형광염색 패널들의 발현을 통하여 제자리 편평세포암과 각질가시세포종이 암의 전구 병변 또는 암에 가까운지에 대한 특성을 파악하여 향후 유망한 생물학적 지표로서의 가능성이 있음을 확인하였다.