Growing evidence suggests that the efficacy of immunotherapy in non-small cell lung cancers (NSCLCs) is associated with the immune microenvironment within the tumor. We aimed to explore radiologic phenotyping using a radiomics approach to assess the immune microenvironment in NSCLC. Two independent NSCLC cohorts (training and test sets) were included. Single-sample gene set enrichment analysis was used to determine the tumor microenvironment, where type 1 helper T (Th1) cells, type 2 helper T (Th2) cells, and cytotoxic T cells were the targets for prediction with computed tomographic (CT) radiomic features. Multiple algorithms were in the modeling followed by final model selection. The training dataset comprised 89 NSCLCs and the test set included 60 cases of lung squamous cell carcinoma and adenocarcinoma. A total of 239 CT radiomic features were used. A linear discriminant analysis model was selected for the final model of Th2 cell group prediction. The area under the curve value of the final model on the test set was 0.684. Predictors of the linear discriminant analysis model were skewness (total and outer pixels), kurtosis, variance (subsampled from delta [subtraction inner pixels from outer pixels]), and informational measure of correlation. The performances of radiomics on test set of Th1 and cytotoxic T cell were not accurate enough to be predictable. A radiomics approach can be used to interrogate an entire tumor in a noninvasive manner and provide added diagnostic value to identify the immune microenvironment of NSCLC, in particular, Th2 cell signatures.

Trichophyton usually causes a superficial skin infection, affecting the outermost layer of the epidermis, the stratum corneum. In immunocompromised patients, deeper invasion into the dermis and even severe systemic infection with distant organ involvement can occur. Most cases of deeper dermal dermatophytosis described in the literature so far involved pre-existing superficial dermatophytosis. We report a 68-year-old woman presented to our clinic with a 3-month history of palpable nodules on the right ankle without pre-existing superficial dermatophytosis. Magnetic resonance imaging showed multiple, well-demarcated, cystic lesions around the lateral malleolus, located in the subcutaneous or dermal layers. The sizes varied from 0.5 cm to 4 cm in diameter. The patient underwent complete excision of the lesions. Fungal culture yielded Trichophyton rubrum on Sabouraud dextrose agar. Histopathology showed organizing abscesses with degenerated fungal hyphae. After the 12-week oral itraconazole therapy, the lesions were completely resolved. Dermatophytes should be considered as a possible cause of deep soft tissue abscesses in immunocompromised patients, even though there is no superficial dermatophytosis lesion.

Accurate molecular classification of breast core needle biopsy (CNB) tissue is important for determining neoadjuvant systemic therapies for invasive breast cancer. The researchers aimed to evaluate the concordance rate (CR) of molecular subtypes between CNBs and surgical specimens. This study was conducted with invasive breast cancer patients who underwent surgery after CNB at Seoul St. Mary's Hospital between December 2014 and December 2017. Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki67 were analyzed using immunohistochemistry. ER and PR were evaluated by Allred score (0-8). HER2 was graded from 0 to +3, and all 2+ cases were reflex tested with silver in situ hybridization. The labeling index of Ki67 was counted by either manual scoring or digital image analysis. Molecular subtypes were classified using the above surrogate markers. In total, 629 patients were evaluated. The CRs of ER, PR, HER2, and Ki67 were 96.5% (kappa, 0.883; p<.001), 93.0% (kappa, 0.824; p<.001), 99.7% (kappa, 0.988; p<.001), and 78.7% (kappa, 0.577; p<.001), respectively. Digital image analysis of Ki67 in CNB showed better concordance with Ki67 in surgical specimens (CR, 82.3%; kappa, 0.639 for digital image analysis vs. CR, 76.2%; kappa, 0.534 for manual counting). The CRs of luminal A, luminal B, HER2, and triple negative types were 89.0%, 70.0%, 82.9%, and 77.2%, respectively. CNB was reasonably accurate for determining ER, PR, HER2, Ki67, and molecular subtypes. Using digital image analysis for Ki67 in CNB produced more accurate molecular classifications.

One of the two copies of the X chromosome is randomly inactivated in females as a means of dosage compensation. Loss of X chromosome inactivation (XCI) is observed in breast and ovarian cancers, and is frequent in basal-like subtype and BRCA1 mutation-associated breast cancers. We investigated the clinical implications of the loss of XCI in ovarian cancer and the association between the loss of XCI and BRCA1 dysfunction. We used open source data generated by The Cancer Genome Atlas (TCGA) Genome Data Analysis Centers. Ward’s hierarchical clustering method was used to classify the methylation status of the X chromosome. We grouped 584 high grade serous ovarian adenocarcinomas (HG-SOA) according to methylation status, loss of heterozygosity and deletion or gain of X chromosome into the following five groups: preserved inactivated X chromosome (Xi) group (n = 175), partial reactivation of Xi group (n = 100), p arm deletion of Xi group (n = 35), q arm deletion of Xi group (n = 44), and two copies of active X group (n = 230). We found four genes (XAGE3, ZNF711, MAGEA4, and ZDHHC15) that were up-regulated by loss of XCI. HG-SOA with loss of XCI showed aggressive behavior (overall survival of partial reactivation of Xi group: HR 1.7, 95% CI 1.1–2.5, two copies of active X group: HR 1.4, 95% CI 1.0–1.9). Mutation and hypermethylation of BRCA1 were not frequent in HG-SOA with loss of XCI. Loss of XCI is common in HG-SOA and is associated with poor clinical outcome. The role of BRCA1 in loss of XCI might be limited. XCI induced aberrant expression of cancer-testis antigens, which may have a role in tumor aggressiveness.

We investigated the clinical implications of biallelic loss of PTEN in clear cell renal cell carcinoma and whether PTEN biallelic loss would induce p53 dependent cellular senescence. Data were obtained using the CGDS-R package from the TCGA data set kirc_tcga_pub. PTEN allelic status was classified into 3 groups, including biallelic PTEN loss (homozygous deletion or combined heterozygous deletion and mutation), monoallelic PTEN loss (heterozygous deletion or mutation) and absent allelic loss. Univariate and multivariate overall survival analysis was performed. TP53 allelic loss and mean expression of genes related to p53 dependent cellular senescence were compared. Of 416 patients with clear cell renal cell carcinoma 11 (2.6%) had biallelic PTEN loss and 69 (16.6%) had monoallelic loss. PTEN allelic loss was associated with late tumor stage and high histological grade. Patients with biallelic loss showed worse overall survival after adjusting for age and AJCC tumor stage (HR 3.1, 95% CI 1.4-6.8, p = 0.005). About half of the patients with PTEN biallelic loss had accompanying TP53 allelic loss. Biallelic loss of PTEN did not increase the expression of genes related to p53 dependent cellular senescence. PTEN biallelic loss may be a prognostic marker for clear cell renal cell carcinoma. It does not seem to induce p53 dependent cellular senescence, partly due to allelic loss of TP53.