Breast cancer is the most common malignancy affecting women, but the heterogeneity of the condition is a significant obstacle to effective treatment. Triple negative breast cancers (TNBCs) do not express HER2 or the receptors for estrogen or progesterone, and so often have a poor prognosis. Tumor-infiltrating T cells have been well-characterized in TNBC, and increased numbers are associated with better outcomes; however, the potential roles of B cells and plasma cells have been large. Here, we conducted a retrospective correlative study on the expression of B cell/plasma cell-related genes, and the abundance and localization of B cells and plasma cells within TNBCs, and clinical outcome. We analyzed 269 TNBC samples and used immunohistochemistry to quantify tumor-infiltrating B cells and plasma cells, coupled with NanoString measurement of expression of immunoglobulin metagenes. Multivariate analysis revealed that patients bearing TNBCs with above-median densities of CD38+ plasma cells had significantly better disease-free survival (DFS) (HR = 0.44; 95% CI 0.26–0.77; p = 0.004) but not overall survival (OS), after adjusting for the effects of known prognostic factors. In contrast, TNBCs with higher immunoglobulin gene expression exhibited improved prognosis (OS p = 0.029 and DFS p = 0.005). The presence of B cells and plasma cells was positively correlated (p < 0.0001, R = 0.558), while immunoglobulin gene IGKC, IGHM, and IGHG1 mRNA expression correlated specifically with the density of CD38+ plasma cells (IGKC p < 0.0001, R = 0.647; IGHM p < 0.0001, R = 0.580; IGHG1 p < 0.0001, R = 0.655). Interestingly, after adjusting the multivariate analysis for the effect of intratumoral CD38+ plasma cell density, the expression levels of all three genes lost significant prognostic value, suggesting a biologically important role of plasma cells. Last but not least, the addition of intratumoral CD38+ plasma cell density to clinicopathological features significantly increased the prognostic value for both DFS (ΔLRχ2 = 17.28, p = 1.71E−08) and OS (ΔLRχ2 = 10.03, p = 6.32E−08), compared to clinicopathological features alone. The best combination was achieved by integrating intratumoral CD38+ plasma cell density and IGHG1 which conferred the best added prognostic value for DFS (ΔLRχ2 = 27.38, p = 5.22E−10) and OS (ΔLRχ2 = 21.29, p = 1.03E−08). Our results demonstrate that the role of plasma cells in TNBC warrants further study to elucidate the relationship between their infiltration of tumors and disease recurrence.

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Head and neck cutaneous squamous cell carcinoma (HNcSCC) can present with cervical metastases without an obvious primary. Immunohistochemistry for p16 is established as a surrogate marker of human papillomavirus (HPV) in oropharyngeal cancer. p16 expression in HNcSCC needs to be elucidated to determine its utility in predicting the primary site. The aim of this study was to evaluate the rate of p16 expression in HNcSCC and its association with prognostic factors and survival. p16 immunohistochemistry was performed on 166 patients with high risk HNcSCC (2000-2013) following histopathology review. Chromogenic in situ hybridisation (CISH) for HPV was performed. Fifty-three (31.9%) cases showed strong, diffuse nuclear and cytoplasmic p16 expression including 14 (41%) non-metastatic and 39 (29.5%) metastatic tumours (p=0.21). HPV CISH was negative in all cases. p16 expression significantly increased with poorer differentiation (p=0.033), but was not associated with size (p=0.30), depth of invasion (p=0.94), lymphovascular invasion (p=0.31), perineural invasion (p=0.69), keratinisation (p=0.99), number of involved nodes (p=0.64), extranodal extension (p=0.59) or survival. Nearly 32% of HNcSCCs, particularly poorly differentiated HNcSCCs, show p16 expression. A primary HNcSCC should be considered in p16 positive neck node metastases in regions with high prevalence of HNcSCC. p16 expression is not associated with improved survival in HNcSCC.

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