CD49f Can Act as a Biomarker for Local or Distant Recurrence in Breast Cancer / 한국유방암학회지

PURPOSE: Metastasis and local recurrence are the primary causes of treatment failure and patient death in breast cancer. The aim of this study was to validate a metastasis- and local recurrenceassociated biomarker for prognostic evaluation and planning treatment strategies. METHODS: Formalin-fixed, paraffin-embedded tissues from a cohort of 312 patients (all stage II and III) were used. The prevalence of CD49f⁺ cells in the patients' tumors was analyzed and correlated with clinical characteristics to determine its prognostic and clinical implications. RESULTS: CD49f⁺ tumor cells were found in a minority of tumors, with 62.8% of the samples showing not a single cell of this subtype. In the clinical characteristics analysis, which were performed with t-tests, CD49f⁺ tumors were not associated with age, tumor size, World Health Organization grade, nodal status, human epidermal growth factor receptor 2 status, progesterone receptor status, or estrogen receptor status, although they were significantly associated with disease recurrence (distant metastasis or/and local recurrence). Univariate survival analysis using the Kaplan-Meier method showed that CD49f⁺ tumors were associated with markedly decreased disease-free survival (DFS); the same result was found using multivariate Cox analysis, even when only chemotherapy-treated patients were analyzed. CONCLUSION: Our results indicated that breast tumors with CD49f⁺ cancer cells are associated with an increased risk for disease recurrence after initial surgery with poor clinical outcomes (decreased DFS). Therefore, as it requires testing for only one additional protein, adding CD49f testing to conventional surgical pathology is a strategy that has great potential for prognostic and treatment-guidance purposes.

Polymorphisms of Integrin, Alpha 6 Contribute to the Development and Neurologic Symptoms of Intracerebral Hemorrhage in Korean Population

OBJECTIVE: The extracellular matrix (ECM) and cell adhesion molecules play crucial roles in angiogenesis, apoptosis, thrombosis, and inflammation, and also contribute to the pathogenesis of stroke. Integrin, alpha 6 (ITGA6) is a member of ECM adhesion receptors. We investigated whether two single nucleotide polymorphisms (SNPs) (rs11895564, Ala380Thr; rs2293649, Asp694Asp) of ITGA6 were associated with the development and clinical phenotypes of intracerebral hemorrhage (ICH) and ischemic stroke (IS). METHODS: We enrolled 199 stroke (78 ICH and 121 IS) and 291 control subjects. Stroke patients were divided into subgroups according to the scores of the National Institutes of Health Stroke Survey (NIHSS, or =6) and Modified Barthel Index (MBI, or =60). SNPStats, SNPAnalyzer, and Helixtree programs were used to calculate odds ratios, 95% confidence intervals, and p values. Multiple logistic regression models were used to analyze genetic data. RESULTS: A missense SNP rs11895564 was associated with the development of ICH (p=0.026 in codominant2, p=0.013 in recessive, p=0.02 in log-additive models; p=0.041 in allele distributions). The A allele frequency of rs11895564 was higher in the ICH group (13.5%) than in the control group (8.1%). In the clinical phenotypes, rs11895564 and rs2293649 showed significant associations in the MBI scores of IS (p=0.014 in codominant1 model; p=0.02 in allele distributions) and NIHSS scores of ICH (p=0.017 in codominant2, p=0.035 in recessive, p=0.035 in log-additive models), respectively. CONCLUSION: These results suggest that ITGA6 may be associated with the development and clinical phenotypes of stroke in Korean population.

Expression of CD151 c-Met, integrin alpha 3, alpha 6 and the prognostic significance in pancreatic ductal adenocarcinoma / 中华胰腺病杂志

Objective To investigate the expression and prognostic significance of CD151, c-Met and integrin alpha 3, alpha6 in pancreatic ductal adenocarcinoma (PDAC). Methods The expression of CD151, c-Met and integrin alpha3, alpha6 in 71 patients with PDAC and 10 samples of normal pancreas tissues were detected by immunohistochemistry, and the relationship between the expression of CD151, c-Met and integrin alpha 3, alpha 6 and the clinicopathological features, prognosis of these patients was analyzed. Results The positive expression rates of CD151, c-Met and integrin alpha 3, alpha 6 in PDAC were 81.69% (58/71) , 69.01% (49/71), 69.01% (49/71) and 84.51% (60/71) , and there was no expression in normal pancreas tissues. The expressions of CD151, c-Met were significantly associated with TNM stage and lymph node metastasis (P < 0.05). The expression of CD151 was positively correlated with the expressions of c-Met and integrin alpha3, alpha6 (r =0.583, P =0.000, r = 0.457;P =0.000, r = 0.671 ;P =0.000). Univariate analysis suggested the expression of CD151, c-Met and integrin alpha3, alpha6 was associated with survival (P<0.05). Multivariate analysis suggested the expression of CD151, c-Met was the independent prognostic factor for post-operative survival. Conclusions CD151, c-Met and integrin alpha3, alpha6 play a role in the development, metastasis and prognosis of PDAC, and they might be new markers to predict biological behavior and the prognosis of PDAC patients.

Hair Follicular Expression of Integrin Alpha-6 Subunit and p63 in Hair Loss / 대한피부과학회지

BACKGROUND: Integrins have a crucial function in the attachment of cells to the extracellular matrix and as important transducers of signals from the extracellular matrix to the matrix cells of the hair follicle. Recent evidence has suggested that p63 is essential for the development of epidermis and skin appendages. OBJECTIVE: To investigate the possibility that integrin alpha-6 and p63 may be involved in the pathogenesis of various conditions of hair loss. METHODS: The expressions of integrin alpha-6 subunit and p63 were examined by immunohistochemical staining of 76 scalp biopsy samples, including 21 male pattern hair loss (MPHL), 19 female pattern hair loss (FPHL), 23 alopecia areata (AA) and 13 female telogen effluvium (TE). In each staining section, the percentage of positive cells and the localization of expression were evaluated. RESULTS: Among the four hair loss groups, MPHL and AA showed nearly negative immunoreactivities of alpha-6 integrin in the basal sides of follicle epithelium. On the other hand, TE immunoreactivity represented very similar pattern of normal control and FPHL samples showed weak outer root sheath staining which was definitely different from that of MPHL. Immunohistochemical staining of p63 in AA and TE revealed relatively strong reactivity compared to MPHL and FPHL. Interestingly, TE p63 immunoreactivity was mainly confined to inner 2/3 outer root sheath. CONCLUSION: These data may explain the somewhat causal and developmental role of integrin alpha-6 and p63 in the occurrence of hair loss. Since both integrin alpha-6 and p63 are necessary for hair follicle growth and maintenance, it is worthwhile taking more concern over these proteins.