Tumor PD-L1 expression is associated with improved survival and lower recurrence risk in young women with oral cavity squamous cell carcinoma.

Young patients with oral cavity squamous cell carcinoma (OCSCC) are often recognized as a distinct epidemiological cohort. In this study, genomic and immune-based metrics were correlated with long-term outcomes for a young patient population treated at a single institution. A fully clinically annotated, retrospective cohort of 81 patients aged ≤45 years with OCSCC is described, and the impact of clinicopathological features on long-term survival outcomes is reported. Genomic and immune parameters were integrated utilizing a whole-exome sequencing and immunohistochemical approach among females in the cohort. It was found that young OCSCC patients had favorable outcomes (10-year disease-free survival 79.1%, overall survival 80.0%) regardless of sex, particularly if they presented with oral tongue primaries and early stage disease. While mutational analysis appeared similar to that of older patients with OCSCC who lack a smoking history, a comparatively high degree of PD-L1 expression and PD-1/L1 concordance (P=0.001) was found among young female OCSCC patients. Subjects with greater membranous PD-L1 positivity and the presence of tumor-infiltrating lymphocytes had a decreased risk of recurrence (P=0.01 and P=0.01, respectively) and improved survival (P=0.04 and P=0.03, respectively). These findings warrant further validation and support the investigation of immunotherapeutic approaches targeting PD-1/L1 interactions in young OCSCC patients.

Reexamining treatment of high-grade T1 bladder cancer according to depth of lamina propria invasion: a prospective trial of 200 patients.

BACKGROUND: Management of high-grade T1 (HGT1) bladder cancer represents a major challenge. We studied a treatment strategy according to substaging by depth of lamina propria invasion. METHODS: In this prospective observational cohort study, patients received initial transurethral resection (TUR), mitomycin-C, and BCG. Subjects with shallower lamina propria invasion (HGT1a) were followed without further surgery, whereas subjects with HGT1b received a second TUR. Association of clinical and histological features with outcomes (primary: progression; secondary: recurrence and cancer-specific survival) was assessed using Cox regression. RESULTS: Median age was 71 years; 89.5% were males, with 89 (44.5%) cases T1a and 111 (55.5%) T1b. At median follow-up of 71 months, disease progression was observed in 31 (15.5%) and in univariate analysis, substaging, carcinoma in situ, tumour size, and tumour pattern predicted progression. On multivariate analysis only substaging, associated carcinoma in situ, and tumour size remained significant for progression. CONCLUSIONS: In HGT1 bladder cancer, the strategy of performing a second TUR only in T1b cases results in a global low progression rate of 15.5%. Tumours deeply invading the lamina propria (HGT1b) showed a three-fold increase in risk of progression. Substaging should be routinely evaluated, with HGT1b cases being thoroughly evaluated for cystectomy. Inclusion in the TNM system should also be carefully considered.

Loss of imprinting in disease progression in chronic myelogenous leukemia.

The pathophysiologic role of the Philadelphia chromosome translocation in chronic myelogenous leukemia (CML) has been known for nearly 20 years. However, the most significant morbidity and mortality in CML are caused by progression to blast crisis, about which comparatively little is known at the molecular level. Genomic imprinting is a chromosomal modification leading to parental-origin-specific gene expression in somatic cells. Recently, we and others have described loss of imprinting (LOI) of the insulin-like growth factor-II gene (IGF2), leading to biallelic rather than monoallelic expression in a wide variety of solid tumors. We have now examined the imprinting status of IGF2 in samples from CML patients in stable phase, accelerated phase, and blast crisis. Five of six stable-phase patients showed normal imprinting, but LOI was found in all six cases of advanced disease (three accelerated phase, three blast crisis), which was statistically highly significant (P < .01). Thus, LOI represents a novel type of genetic alteration in CML that appears to be specifically associated with disease progression.