Tumor-infiltrating lymphocyte (TIL), programmed death-ligand 1 (PD-L1) expression and neutrophil-to-lymphocyte ratio (NLR) is associated to immunogenicity and prognosis of breast cancer. We analyzed baseline NLR, changes of NLR, TIL, and PD-L1 during neoadjuvant chemotherapy (NAC) and their clinical implication in triple-negative breast cancer (TNBC). Between January 2008 to December 2015, 358 TNBC patients were analyzed. Baseline NLR, 50 paired NLR (initial diagnosis, after completion of NAC) and 34 paired tissues (initial diagnosis, surgical specimen after completion of NAC) were collected. Changes of TIL, CD4, CD8, forkhead box P3 (FOXP3), and PD-L1 expression were assessed with immunohistochemical stain. Low NLR (≤ 3.16) was associated to superior survival (overall survival: 41.83 months vs. 36.5 months, p=0.002; disease-free survival [DFS]: 37.85 months vs. 32.14 months, p=0.032). Modest NLR change after NAC (-30% < NLR change < 100%) showed prolonged DFS (38.37 months vs. 22.37 months, p=0.015). During NAC, negative or negative conversion of tumor PD-L1 expression was associated to poor DFS (34.77 months vs. 16.03 months, p=0.037), and same or increased TIL showed trends for superior DFS, but without statistical significance. Positive tumor PD-L1 expression (H-score ≥ 5) in baseline or post- NAC tissue was associated to superior DFS (57.6 months vs. 12.5 months, p=0.001 and 53.3 months vs. 18.9 months, p=0.040). Positive stromal PD-L1 expression in baseline was also associated to superior DFS (50.2 months vs. 20.4 months, p=0.002). In locally advanced TNBC, baseline NLR, changes of NLR during NAC was associated to survival. Baseline PD-L1 expression and changes of PD-L1 expression in tumor tissue during NAC also showed association to prognosis.

Hypoxia in the tumor microenvironment is the leading factor in angiogenesis. Angiogenesis can be identified by dynamic contrast-enhanced breast MRI (DCE MRI). Here we investigate the relationship between perfusion parameters on DCE MRI and angiogenic and prognostic factors in patients with invasive ductal carcinoma (IDC). Perfusion parameters (K^trans, k_ep and v_e) of 81 IDC were obtained using histogram analysis. Twenty-fifth, 50th and 75th percentile values were calculated and were analyzed for association with microvessel density (MVD), vascular endothelial growth factor (VEGF) and conventional prognostic factors. Correlation between MVD and v_e50 was positive (r = 0.33). K^trans₅₀ was higher in tumors larger than 2 cm than in tumors smaller than 2 cm. In multivariate analysis, K^trans₅₀ was affected by tumor size and MVD with 12.8% explanation. There was significant association between K^trans₅₀ and tumor size and MVD. Therefore we conclude that DCE MRI perfusion parameters are potential imaging biomarkers for prediction of tumor angiogenesis and aggressiveness.

Colorectal adenocarcinoma, the most common tumor that metastasizes to the ovary, is often difficult to distinguish from primary ovarian mucinous adenocarcinoma (POMA). Obtaining the correct diagnosis is difficult but crucial to treatment and prognosis. We evaluated the immunohistochemical (IHC) expression of cytokeratin 7 (CK7), cytokeratin 20 (CK20), CDX2, CEA, MUC2, MUC5AC and α-methylacyl-CoA racemase (AMACR) in 22 POMAs and 41 metastatic colorectal adenocarcinomas (MCAOs) involving ovaries. MCAOs, in contrast with POMAs, were almost always negative for MUC5 (97.6%), often negative for CK7 (82.9%), focal or diffuse positive for CDX2 (73.2%), diffuse positive for CK20 (65.9%), focal or diffuse positive for MUC2 (51.2%), diffuse positive for CEA (41.5%) and negative for AMACR (41.5%). We therefore considered CK7 (−), CK20 (diffuse +), CDX2 (+) and MUC2 (+) to be colonic markers and regarded cases with expression of more than two colonic markers as MCAO, those with no expression of colonic markers as POMA and those with expression of one colonic marker as indeterminate. Using CK7/CK20/CDX2/MUC2, 82.5% of the cases were correctly classified, 6.3% were misclassified and 6.3% were indeterminate. CK7, CK20, CDX2 and MUC2 IHC staining is a useful adjunctive diagnostic tool to differentiate MCAOs from POMAs, in addition to clinical history and gross and microscopic findings.

Targeted next-generation sequencing (NGS) technology detects specific mutations that can provide treatment opportunities for colorectal cancer (CRC) patients. We included 145 CRC patients who underwent surgery. We analyzed the mutation frequencies of common actionable genes and their association with clinicopathological characteristics and oncologic outcomes using targeted NGS. Approximately 97.9% (142) of patients showed somatic mutations. Frequent mutations were observed in TP53 (70%), APC (60%), and KRAS (49%). TP53 mutations were significantly linked to higher overall stage (p = 0.038) and lower disease-free survival (DFS) (p = 0.039). ATM mutation was significantly associated with higher tumor stage (p = 0.012) and shorter overall survival (OS) (p = 0.041). Stage 3 and 4 patients with ATM mutations (p = 0.023) had shorter OS, and FBXW7 mutation was significantly associated with shorter DFS (p = 0.002). However, the OS of patients with or without TP53, RAS, APC, PIK3CA, and SMAD4 mutations did not differ significantly (p = 0.59, 0.72, 0.059, 0.25, and 0.12, respectively). Similarly, the DFS between patients with RAS, APC, PIK3CA, and SMAD4 mutations and those with wild-type were not statistically different (p = 0.3, 0.79, 0.13, and 0.59, respectively). In multivariate Cox regression analysis, ATM mutation was an independent biomarker for poor prognosis of OS (p = 0.043). A comprehensive analysis of the molecular markers for CRC can provide insights into the mechanisms underlying disease progression and help optimize a personalized therapy.

Background: Percutaneous core needle biopsy (CNB) is considered to be the standard technique for histological diagnosis of breast lesions. But, it is less reliable for diagnosing atypical ductal hyperplasia (ADH). The purpose of the present study was to predict, based on clinical and radiological findings, which cases of ADH diagnosed by CNB would be more likely to be associated with a more advanced lesion on subsequent surgical excision. Methods: Between February 2002 and December 2007, consecutive ultrasound-guided CNBs were performed on suspicious breast lesions at Seoul St. Mary's Hospital. A total of 69 CNBs led to a diagnosis of ADH, and 45 patients underwent follow-up surgical excision. We reviewed the medical records and analyses retrospectively. Results: Sixty-nine patients were diagnosed with ADH at CNB. Of these patients, 45 underwent surgical excision and 10 (22.2%) were subsequently diagnosed with a malignancy (ductal carcinoma in situ, n = 8; invasive cancer, n = 2). Univariate analysis revealed age (≥ 50-years) at the time of core needle biopsy (p = 0.006), size (> 10 mm) on imaging (p = 0.033), and combined mass with microcalcification on sonography (p = 0.029) to be associated with underestimation. When those three factors were included in multivariate analysis, only age (p = 0.035, HR 6.201, 95% CI 1.135-33.891) was an independent predictor of malignancy. Conclusion: Age (≥ 50) at the time of biopsy is an independent predictive factor for breast cancer at surgical excision in patients with diagnosed ADH at CNB. For patients diagnosed with ADH at CNB, only complete surgical excision is the suitable treatment option, because we could not find any combination of factors that can safely predict the absence of DCIS or invasive cancer in a case of ADH.

An YY, et al. J Korean Med Sci. 2015 Jun;30(6):808-815. https://doi.org/10.3346/jkms.2015.30.6.808