Background Progress in radiation treatment of head and neck squamous cell carcinoma (HNSCC) deserves the studies focused on molecular predictors that would help to enhance individually tailored treatment. Methods p16/epidermal growth factor receptor (EGFR)/cluster of differentiation‐44 (CD44) was immunohistochemically analyzed in 165 HNSCC patients. Results In the entire group and the p16 negative cohort, better 3‐year overall survival and locoregional control correlated with p16 positivity, CD44, and EGFR negativity were observed. Combined analysis revealed the worst results in the CD44+/p16−, EGFR+/p16−, and EGFR+/CD44+ groups and in the EGFR+/CD44+ within p16 negative cohort. Multivariate analysis found tumor stage, Karnofsky index, p16, and CD44 as prognostic factors of overall survival and clinical stage, and p16 as a prognostic factor for locoregional control. Clinical stage and Karnofsky index affected overall survival and tumor stage. EGFR affected locoregional control in the p16 negative subgroup. Conclusion Our study confirmed the negative effect of CD44 and EGFR and the positive effect of p16 on radiotherapy results.

Background: We examined PD-L1 expression on tumor cells (TCs) and immune cells (ICs) and density of CD3 + and CD8 + tumor-infiltrating lymphocytes (TILs) in patients with oropharyngeal squamous cell carcinoma (OPSCC) and investigated their significance on clinicopathological characteristics and clinical outcomes. Methods: In a cohort of 65 patients treated by definitive intensity-modulated radiotherapy (IMRT) with curative intent, immunohistochemical analysis of PD-L1 expression on TCs and ICs, and TIL subtyping was performed on primary biopsy tumor tissues, followed by prognostic evaluation of these immune response-related parameters including classification into four tumor immune microenvironment (TIM) types. To evaluate HPV status, p16 immunohistochemistry was performed. Results: Densities of CD3 + and CD8 + TILs and PD-L1 expressions on TCs and ICs were significantly higher in p16+/HPV-mediated OPSCC. Patients with high densities of stromal CD8 + TILs displayed significantly better overall survival (OS) and progression-free survival (PFS). PD-L1 expression neither on tumor cells nor on immune cells affected survival outcomes. Distribution of TIM types based on the combination of PD-L1 expression on TCs and densities of CD8 + TILs is significantly different in p16+ compared with p16-OPSCC. In type III TIM (TC-PD-L1+/low CD8 + TIL density), significantly better OS was shown in p16+ group compared with p16-OPSCC. Conclusion: The prognostic and predictive role of tumor immune microenvironment was confirmed for patients with OPSCC. Combining HPV status with the evaluation of densities of CD8 + TILs and PD-L1 expression including TIM classification might be of high clinical interest and warrants further prospective evaluation.

Aims. Tumor-associated macrophages (TAMs) are known markers playing complex roles in tumorigenesis. However, the function of TAMs in a variety of malignancies is not yet fully understood. The aim of this pilot study was to quantify the density of TAMs in Ewing sarcoma and to determine the correlation between TAMs and clinicopathological parameters. Methods. Using immunohistochemistry, the expressions of CD68 and CD163 were examined in 24 tissue samples of Ewing sarcoma of bone. The density of CD68 and CD163-positive TAMs was analyzed quantitatively and semi-quantitatively and statistically correlated with clinical parameters. Results. CD163-positive TAMs outnumbered CD68-positive cells (median of 130 vs 96, respectively). No statistically significant relatio nship was found between density of CD68-positive cells, clinical parameters or prognosis. However, high levels of CD163-positive TAMs were associated with localized disease (P=0.008). In cases with a higher density of CD163-positive cells, a trend toward longer survival was revealed (P=0.063). Conclusion. This is the first study that has quantified CD163 expression in TAMs in Ewing sarcoma and showed its possible prognostic value. CD163 was confirmed to be a more specific marker of macrophages than CD68. CD163 is not an exclusive hallmark of M2 macrophages.

1 I. ústav patologie, LF MU a FN u sv. Anny v Brně 2 Klinika radiační onkologie, LF MU a Masarykův onkologický ústav, Brno 3 CEITEC -Středoevropský technologický institut, MU, Brno 4 Klinika komplexní onkologické péče, LF MU a Masarykův onkologický ústav, Brno SouhrnVýchodiska: Karcinomy orofaryngu asociované s lidským papilomavirem (human papillomavirus -HPV) nejen pro svou nadále vzrůstající incidenci představují významnou kapitolu v oblasti nádorů hlavy a krku. Tyto nádory oproti HPV negativním karcinomům orofaryngu disponují odlišnými epidemiologickými, klinickými i molekulárními vlastnostmi, lepší odpovědí na léčbu a prognózou. Vlivem těchto skutečností byla provedena celá řada studií, jejichž společným cílem bylo navržení adekvátního stagingového systému pro HPV asociované karcinomy orofaryngu, neboť 7. vydání American Joint Committee on Cancer nebralo v potaz unikátní bio logické chování tohoto onemocnění. Výsledkem jsou zásadní změny v TNM klasifikaci karcinomů orofaryngu, které jsou nyní v závislosti na expresi surogátního markeru high-risk HPV p16 členěny na p16 pozitivní a p16 negativní. Cíl: Cílem tohoto přehledového článku je nejen shrnutí aktuálních vědomostí o HPV asociovaných karcinomech orofaryngu s důrazem na jejich molekulární podklad a morfologii, ale také shrnutí a porovnání metod detekce viru HPV. Zároveň je diskutován prognostický význam exprese biomarkeru p16 u těchto nádorů. Součástí přehledového článku je dále představení změn ve stagingu karcinomů orofaryngu v závislosti na expresi markeru p16, vč. odůvodnění, která k těmto změnám vedla. SummaryBackground: The incidence of oropharyngeal carcinomas associated with human papillomavirus (HPV) is continuously increasing. HPV-positive and -negative oropharyngeal carcinomas have different epidemiological, clinical, and molecular features, with HPV-positive tumors having a better response to treatment and better prognosis. An adequate staging system for HPV-related oropharyngeal carcinomas is needed, as the American Joint Committee on Cancer 7 th Edition did not consider their unique bio logical behavior. At present, oropharyngeal carcinomas are subdivided into p16 positive and p16 negative tumors, based on their expression of p16, a surrogate marker of high--risk HPV. Purpose: This review summarizes current knowledge of HPV-associated oropharyngeal carcinomas with emphasis on their molecular features and histopathology, as well as summarizes and compares HPV detection methods and genotyping techniques. This review also describes the prognostic significance of p16 expression in these tumors and significant changes in the staging of oropharyngeal carcinomas based on p16 expression, together with the justifications for these changes.

Combined immunoprofiles of p16, EGFR, and CD44 might provide valuable prognostic and predictive information for the individual OPSCC patients, especially in terms of response to IMRT and prediction of treatment outcomes. Application of the AJCC 8th edition staging for HPV+ OPSCC proved to improve hazard discrimination and prognostication of OPSCC.

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