Altered Immunohistochemical Expression Patterns of HLA Class I during the Clinical Course of Cervical Intraepithelial Neoplasia

It is unclear how immunohistochemical expression patterns of HLA class I in the pre-malignant phase of cervical intraepithelial neoplasia (CIN) alter during the clinical follow-up period. The present study aimed to demonstrate the correlation between the immunohistochemical expression pattern of HLA class I and the CIN grade through repeated examinations during the clinical course. Expression patterns of HLA class I, p16INK4a, and PD-L1 were immunohistochemically examined using formalin-fixed paraffin-embedded (FFPE) sections of biopsy or conization samples that were obtained from 20 patients diagnosed with CIN. The mRNA expression levels of HLA class I were analyzed by real-time reverse transcription polymerase chain reaction using FFPE sections of 14 patients, who were examined metachronously during the follow-up period. HLA class I expression was limited to the lower part of the epithelial thickness (M1 pattern) in more than half of CIN1 cases, and was present throughout the epithelial thickness (M2 pattern) in one fourth of CIN1 and CIN2 cases approximately. Heterogeneous expression (H pattern) was detected in half of CIN2 and CIN3 cases and in the all of squamous cell carcinoma cases. Metachronous examinations revealed that these immunohistochemical patterns altered more frequently than the CIN grade. The rate of change of HLA class I mRNA expression level was higher in cases with a progressed immunohistochemical pattern compared to those with regressed immunohistochemical pattern. In conclusion, the immunohistochemical pattern of HLA class I expression is associated with the CIN grade, and it is alterable during the clinical course, especially in CIN2.