Systemic inflammatory markers derived from peripheral blood cell, such as the neutrophil-lymphocyte ratio (NLR), derived neutrophil-lymphocyte ratio (dNLR), platelet-lymphocyte ratio (PLR) and lymphocyte-monocyte ratio (LMR), have been demonstrated as prognostic markers in several types of malignancy. Here, we investigated and compared the association between systemic inflammatory markers and survival and developed a prognostic nomogram in breast cancer patients. We reviewed the clinical and pathological records of 661 patients diagnosed with invasive breast carcinoma between 1993 and 2011. The NLR, dNLR, PLR and LMR in the immediate preoperative period were assessed. We analyzed the relationship between these inflammatory markers and clinicopathologic variables, disease-specific survival (DSS), and disease-free survival (DFS) in patients. A nomogram was developed to predict 3- and 5-year DSS for breast cancer. In the univariate analysis, high NLR, dNLR, PLR and low LMR were all significantly associated with poor DSS and DFS. In the multivariate analysis, only the PLR (HR 3.226, 95% CI 1.768–5.885 for DSS and HR 1.824, 95% CI 1.824–6.321 for DFS) was still identified as an independent predictor of outcomes. A subgroup analysis revealed that the PLR was the sole independent marker predicting poor DSS in patients with lymph node metastasis (HR 2.294, 95% CI 1.102–4.777) and with luminal subtype (HR 4.039, 95% CI 1.905–8.562). The proposed nomogram, which includes the PLR, shows good accuracy in predicting DSS with a concordance index of 0.82. PLR is an indicator of systemic inflammation as a part of the host immune response. As an independent prognostic factor, an elevated preoperative PLR is superior to the NLR, dNLR, and LMR in predicting clinical outcomes in patients with breast cancer. Moreover, the nomogram incorporating the PLR could accurately predict individualized survival probability in breast cancer.

Cho U, et al. J Korean Med Sci. 2014 Aug;29(8):1054-1060. https://doi.org/10.3346/jkms.2014.29.8.1054

Background: A high platelet–lymphocyte ratio (PLR) is a marker of systemic inflammation and, together with the neutrophil–lymphocyte ratio (NLR), is associated with poor outcomes in several cancers. We investigated the prognostic value of PLR and other systemic inflammatory markers, such as NLR, systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI), in oral squamous cell carcinoma (OSCC) patients undergoing surgical resection. Methods: We derived PLR, NLR, SII, and SIRI from a retrospective chart review of 269 consecutive OSCC patients. The complete blood count examined in the immediate preoperative period was used to compute PLR, NLR, SII, and SIRI. We analyzed the relationship between these systemic inflammatory markers and the clinicopathologic characteristics, disease-specific survival (DSS), and progression-free survival (PFS) of patients. Results: In the univariate analysis, high PLR and SII were significantly associated with worse DSS and PFS (all p < 0.05). In the multivariate analysis, PLR (HR 2.36, 95% CI 1.28–4.36 for DSS; HR 1.80, 95% CI 1.06–3.06 for PFS) was an independent predictor of survival outcomes. When PLR was analyzed as a continuous variable, the relationship between the outcome and preoperative PLR was not monotonically linear. In the subgroup analysis, PLR was more strongly associated with DSS and PFS in patients who were male, had stage III/IV OSCC, or had lymph node metastasis. Conclusion: Our data suggest that in OSCC patients, the pretreatment PLR is an independent predictor of DSS and PFS. The PLR is a readily available biomarker that will improve prognostication and risk stratification in OSCC.

Human leukocyte antigen class I (HLA-I) molecules play important roles in regulating immune responses. Loss or reduction of HLA-I expression has been shown to be associated with prognosis in several cancers. Regulatory T-cells (Tregs) also play critical functions in immune response regulation. Evaluation of HLA-I expression status by the EMR8-5 antibody and its clinical impact in breast cancer have not been well studied, and its relationship with Tregs remains unclear. We evaluated HLA-I expression and Treg infiltration by immunohistochemistry in 465 surgically resected breast cancer samples. We examined the correlation between HLA-I expression and Treg infiltration and clinicopathologic characteristics and survival analyses were performed. Total loss of HLA-I expression was found in 84 breast cancer samples (18.1%). Univariate survival analysis revealed that loss of HLA-I expression was significantly associated with worse disease-specific survival (DSS) (p = .029). HLA-I was not an independent prognostic factor in the entire patient group, but it was an adverse independent prognostic factor for DSS in patients with advanced disease (stage II-IV) (p = .031). Treg numbers were significantly higher in the intratumoral stroma of HLA-I-positive tumors than in HLA-I-negative tumors (median 6.3 cells/high power field vs 2.1 cells/high power field, p < .001). However, Tregs were not an independent prognostic factor in our cohort. Our findings suggest that the loss of HLA-I expression is associated with poor prognosis in breast cancer patients, highlighting the role of HLA-I alterations in immune evasion mechanisms of breast cancer. HLA-I could be a promising marker that enables the application of more effective and precise immunotherapies for patients with advanced breast cancer.

Squamous cell carcinomas (SqCCs) of the lung are known to arise more often in a central area but reports of peripheral SqCCs have increased, with a pathogenesis that is obscured. In this study, the clinicopathologic characteristics of peripheral lung SqCCs were studied and compared with those of the central type. This study included 63 peripheral lung SqCCs and 48 randomly selected central cases; hematoxylin and eosin-stained slides of surgically resected specimens were reviewed in conjunction with radiologic images and clinical history. Cytokeratin-7 immunohistochemical staining of key slides and epidermal growth factor receptor (EGFR)/KRAS mutations tested by peptide nucleic acid clamping were also included. Stages of peripheral SqCCs were significantly lower than central SqCCs (p=.016). Cystic change of the mass (p=.007), presence of interstitial fibrosis (p=0.007), and anthracosis (p=.049) in the background lung were significantly associated with the peripheral type. Cytokeratin-7 positivity was also higher in peripheral SqCCs with cutoffs of both 10% and 50% (p=.011). Pathogenic mutations in EGFR and KRAS were observed in only one case out of the 72 evaluated. The Cox proportional hazard model indicated a significantly better disease-free survival (p=.009) and the tendency of better overall survival (p=.106) in the peripheral type. In peripheral type, lower stage is a favorable factor for survival but more frequent interstitial fibrosis and older age are unfavorable factors. Multivariate Cox analysis revealed that peripheral type is associated with better disease-free survival. The pathogenesis of peripheral lung SqCCs needs further investigation, together with consideration of the background lung conditions.