JungHan Yoon

The neutrophil to lymphocyte ratio can discriminate anaplastic thyroid cancer against poorly or well differentiated cancer.

Purpose We evaluated the capability of the neutrophil to lymphocyte ratio (NLR) as a diagnostic tool to discriminate between poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) from well differentiated thyroid cancer (WDTC). Methods The NLR of 3,870 patients with benign and malignant thyroid tumors were analyzed. There were 436 benign, 3,364 papillary, 15 medullary, 34 follicular or hurthle type, 14 PDTC, and 7 ATC type neoplasms. Patients were divided into two groups: a high NLR group and a low NLR group. Results The NLR of all 3,870 patients was a normal distribution, and the median value was 1.57. Advanced stage cancer, such as T3 or T4 was high (30.4% vs. 26.5%, P = 0.027), and cancer-specific deaths were also high (1.2% vs. 0.4%, P = 0.018) in the high NLR group. The proportion of PDTC (0.6% vs. 0.1%) and ATC (0.3% vs. 0.1%) was higher in the high NLR group. The NLR can discriminate between PTC, PDTC, and ATC (P = 0.035, P = 0.002, and P = 0.025, respectively), and the cutoff value was 3.8 between PDTC versus ATC. None of the NLR of PDTC exceeded the cutoff value of 3.8. Conclusion NLR can play a relevant role as a discriminating tool and may be considered as a new diagnostic criterion in discriminating as well as in selecting therapeutic approaches to these aggressive forms of thyroid cancer.

Abstract P4-12-11: Up-regulation of SPARC is associated with breast tumor progression and epithelial SPARC expression is correlated with poor survival and MMP-2 expression in patients with breast carcinoma

Background: Secreted protein acidic and rich in cysteine (SPARC) plays a crucial role in the process of tumor invasion and metastasis in many cancers. Matrix metalloproteinases (MMPs) degrade the extracellular matrix and participate in several key processes of invasion and metastasis. The aims of this study were to evaluate the potential involvement of SPARC in the progression of breast tumor and to determine its association with outcome variables and MMPs expression in patients with breast carcinoma (BC). Materials and Methods: SPARC expression was examined in 8 pairs of BC tissues and surrounding normal tissues at mRNA and protein levels by quantitative real-time PCR (qRT-PCR), RNAscope in situ hybridization (ISH), Western blotting, and immunohistochemistry techniques. Immunohistochemical staining of SPARC on tissue microarray was done in 26 normal breasts, 76 ductal carcinoma in situ (DCIS), and 198 BC samples. In addition, we performed immunohistochemical staining for MMP-2 and MMP-9 in BC. Results: SPARC expression at mRNA and protein levels by qRT-PCR and Western blotting was significantly increased in BC tissues compared to the surrounding normal tissues (p Conclusion: Our results suggest that up-regulation of SPARC contributes to breast tumor progression. SPARC expression may be a useful biomarker for the prognostic prediction in patients with BC. SPARC can control extracellular matrix degradation through up-regulation of MMP-2. Citation Format: Lee JS, Kim G-E, Park MH, Yoon JH. Up-regulation of SPARC is associated with breast tumor progression and epithelial SPARC expression is correlated with poor survival and MMP-2 expression in patients with breast carcinoma [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-12-11.

Abstract P2-07-06: Periostin is associated with breast tumor progression and epithelial periostin expression is correlated with poor survival in patients with invasive breast carcinoma

Background: Invasion and metastasis are the direct causes of mortality in patients with breast cancer and require reciprocal interactions between cancer cells and the extracellular matrix (ECM). Periostin, a fasciclin-containing adhesive ECM glycoprotein, is frequently overexpressed in various types of human cancer, and its overexpression in cancer-associated stroma and/or cancer cells is usually associated with poor clinical outcomes. However, the expression of periostin in the successive steps of breast tumorigenesis and its association with outcome variables have not been well established in breast carcinoma. The purposes of the present study were to assess the role of periostin alteration in breast tumorigenesis and evaluate the putative prognostic value of periostin as a function of its compartmentalization. Materials and Methods: Immunohistochemical staining with anti-periostin antibody was performed in a total of 300 patients (26 patients with normal breasts, 76 patients with ductal carcinoma in situ [DCIS], and 198 patients with invasive breast carcinoma [IBC]) using tissue microarray. Periostin immunoreactivity was assessed in both epithelial tissue and the surrounding stromal compartment. In addition, the mRNA and protein expression of periostin was analyzed in 10 paired normal/invasive cancer frozen specimens by quantitative real time-polymerase chain reaction and western blot analysis, respectively. Results: Periostin mRNA and protein expression in cancer tissues was increased compared with that in adjacent normal tissues. Both epithelial and stromal periostin staining scores were significantly increased with disease progression in a stepwise manner to DCIS and IBC compared with those in normal breast tissues (P = 0.000 and 0.000, respectively). High epithelial and stromal periostin expression was observed in 109 of 189 (57.7%) and 158 of 189 (83.6%) cases of IBC, respectively. High epithelial periostin expression was more frequently observed in the distant metastatic relapse-positive group than in the distant metastatic relapse-negative group (41 [80.4%] of 51 cases versus 68 [49.3%] of 138 cases [P = 0.000]). Furthermore, high epithelial periostin expression was associated with reduced disease-free and overall survival on univariate and multivariate analyses. Conclusion: Periostin might play an important role in the progression of breast tumor, and epithelial periostin expression may serve as a new parameter for prognostic prediction in patients with IBC. Further study of periostin expression and its potential as a target of therapy for IBC appears warranted. Citation Format: Lee JS, Kim G-E, Park MH, Yoon JH. Periostin is associated with breast tumor progression and epithelial periostin expression is correlated with poor survival in patients with invasive breast carcinoma. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-07-06.

Abstract P2-10-03: Metastasis-associated in colon cancer 1 predicts poor outcomes in patients with breast cancer

Background: Metastasis-associated in colon cancer 1 (MACC1) plays a role in cancer invasion and metastasis through the upregulation of hepatocyte growth factor/mesenchymal epithelial transition-pathway, which is a known critical regulator of the mitogen-activated protein kinase (MAPK) cascades. However, the potential involvement of MACC1 in breast cancer has not been assessed. Materials and Methods: To investigate whether MACC1 expression is a prognostic marker in breast cancer, we performed immunohistochemical staining for MACC1 expression in tissue microarrays consisting of 198 invasive breast carcinomas. To demonstrate the potential correlation between MACC1 and MAPK cascades, phospho-p44/42 MAPK (ERK1/2) expression was also analyzed. Results: Expression of MACC1 was detected in 109 (55.1%) of 198 invasive breast carcinomas. MACC1 expression was significantly associated with several clinicopathologic parameters, including ER negativity (P Conclusion: Our results suggest that MACC1 may serve as a new parameter for the prognostic prediction in patients with invasive breast carcinoma. MACC1 is likely to be involved in the regulation of MAPK cascades in invasive breast carcinoma. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-10-03.

P2-11-05: Stromal Matrix Metalloproteinase-14 Expression Correlates with the Grade and Biological Behavior of Mammary Phyllodes Tumors.

Phyllodes tumors (PTs) of the breast are rare biphasic tumors with the potential for invasion and metastatic spread. Matrix metalloproteases (MMPs) and their tissue inhibitors of metalloproteases (TIMPs) are involved in several key aspects of tumoral growth, invasion and metastasis, but little is known of their expression in PTs. The objective of this study was to assess the expression of MMPs and TIMPs in PTs and to determine their association with grade and clinical behavior of PTs. Eighty-two PTs (50 benign, 22 borderline, and 10 malignant) were studied. Automated immunohistochemical staining for MMP-1, -2, -7, -9, -11, -13, and -14 and TIMP-1, -2, and -3 was performed using tissue microarray blocks and the expression of MMPs and TIMPs was assessed in both the stromal components. There were no significant differences in the expression of stromal MMPs and TIMPs in the three groups of PTs, except for MMP-14. There was a significant increase in stromal MMP-14 expression with increasing PT grade (P Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-11-05.

P2-11-03: High Expression of CX3CL1 by Tumor Cells Correlates with a Good Prognosis and Increased Infiltrating CD8+ T Cells, Natural Killer Cells, and Dendritic Cells in Breast Carcinoma.

CX3CL1 is the only CX3C chemokine that can chemoattract CD8+ T cells, natural killer (NK) cells, and dendritic cells (DCs). Although studies have reported that CX3CL1 regulates the host immune response, the roles of the CX3CL1 in breast carcinoma remain unknown. We evaluated the expression CX3CL1 in 198 surgical specimens of breast carcinoma and analyzed any association with the clinicopathological factors, including CD8+ T cells, CD56+ NK cells, and CD1a+ DCs, while also evaluating the impact on the prognosis. High CX3CL1 expression was found in 136 of 198 (68.7%) breast carcinomas. The numbers of stromal CD8+ T cells, intratumoral CD1a+ DCs, and stromal CD56+ NK cells were significantly increased in the high CX3CL1 expression group (19.3 ± 15.2, 0.3 ± 0.9 and 1.4 ± 1.7 per field, respectively) compared with the low expression group (10.2 ± 13.1, 0.0 ± 0.3 and 0.7 ± 0.8 per field, respectively). Patients with high CX3CL1 expression had a significantly better prognosis for disease-free and overall survival than those with low expression ( P = 0.002 and P = 0.000, respectively). In a multivariate analysis, the CX3CL1 expression was identified as one of the independent prognostic factors for overall survival (odds ratio, 2.29; P = 0.002). These data suggest that CX3CL1 expressed in the tumor cells appears to enhance the recruitment of CD8+ T cells, NK cells, and CD1a+ DCs, thereby bringing about a better prognosis in breast carcinoma. CX3CL1 is a new prognostic biomarker and be a novel candidate for development of a more effective therapeutic strategy for breast carcinoma. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-11-03.