Prognostic Significance of Immunohistochemical Phenotypes in Patients Treated for High-Grade Cervical Intraepithelial Neoplasia

Abstract

Strong evidence exists that the host's immune system plays a crucial role for the development of human papillomavirus-related cervical premalignant and malignant lesions. In particular, effective cell-mediated immunity (CMI) promotes spontaneous infection clearance and cancer precursors regression in healthy subjects, while immunosuppressed individuals are more likely to experience infection persistence, cervical intraepithelial neoplasia (CIN) lesions, and cervical cancer. In this study, the prognostic significance of immunohistochemical profiling of CD4+ T-cells, CD8+ T-cells, dendritic cells (CD11c+), T-bet+, and GATA-3+ transcription factors has been studied in surgical specimens of 34 consecutive women affected by high-grade cervical intraepithelial neoplasia (CIN2-3) submitted to cervical conization. Results have been correlated with the clinical outcomes at 24 months after treatment and statistically analyzed. Higher rates of CD4+ T-cells, CD11c+ dendritic cells, and T-bet+ transcription factor positivity showed a strong statistically significative correlation with favourable clinical outcomes (P ≤ 0.0001). These data reinforce the evidence of the relevance of the host's immune status in the natural history of HPV-related cervical disease and add a prognostic significance of the cervical immunological profile in terms of predicting significant lower recurrence rates.

Immune Contexture, Immunoscore, and Malignant Cell Molecular Subgroups for Prognostic and Theranostic Classifications of Cancers

“…2). The majority support a positive impact on prognosis associated with extensive memory T-cell infiltration in the same cancers we discussed earlier, eg, CRC (Anitei et al, 2014;Boissi ere-Michot et al, 2014;Correale et al, 2012;Kim, Bae, et al, 2015;Ling et al, 2014;Ong et al, 2015;Shinto et al, 2014), bladder (Ingels et al, 2014), breast de Kruijf et al, 2013;García-Martínez et al, 2014;Kim et al, 2013;Mohammed et al, 2013;Park et al, 2012;Rathore et al, 2014;Seo et al, 2013;West et al, 2013), Merkel cell carcinoma (Paulson et al, 2014), glioma (Han et al, 2014), pancreatic (Ino et al, 2013;Tang et al, 2014), head and neck (Balermpas et al, 2014;Czystowska et al, 2013;Millrud et al, 2012;Wallis et al, 2015), cervical (Origoni et al, 2013), NSCLC Hald et al, 2013), gastric Feichtenbeiner et al, 2014;Kim et al, 2014), ovarian (Bachmayr-Heyda et al, 2013;Nielsen et al, 2012;Preston et al, 2013), and HCC (Cariani et al, 2012;Chen et al, 2012;Guo et al, 2007;Huang et al, 2012) (Table 1 and Fig. 2).…”

Age‐related changes in pre‐ and post‐conization HPV genotype distribution among women with high‐grade cervical intraepithelial neoplasia

“…The present study did not investigate the immunological status of the patients included; other authors have investigated this topic with interesting results. Origoni et al . reported that higher immunohistochemical positivity (CD4+ T‐cells and T‐bet+ transcription factor) in cone specimens was associated with a lower incidence of disease recurrence .…”

“…Origoni et al . reported that higher immunohistochemical positivity (CD4+ T‐cells and T‐bet+ transcription factor) in cone specimens was associated with a lower incidence of disease recurrence . Further, in a study that included patients who had CIN and HIV, it was reported that immunological factors could play an important role in post‐conization outcomes …”

Validation of Intratumoral T-bet+ Lymphoid Cells as Predictors of Disease-Free Survival in Breast Cancer

“…More recently, T-bet has been shown to be required for promoting blockade-induced CD8 þ T-cell effector responses sufficient to eradicate disseminated leukemia in an animal model (26). Furthermore, high numbers of T-bet þ intratumoral lymphoid cells have been found to correlate with improved outcome in gastric cancer (27) and in high-grade cervical intraepithelial neoplasia (28). In a cohort of women with familial breast cancer from the Ontario site of the Breast Cancer Family Registry (29), studied for expression of chemokine CXCL10 and tumoral lymphocytic infiltration, we observed that T-bet þ lymphocytes were associated with the basal molecular subtype as well as with morphologic features characteristic of such tumors, including high-grade, p53 expression, ER negativity, CK5 positivity, and EGFR positivity (30).…”