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Tumoral lymphocytic infiltration and expression of the chemokine CXCL10 in breast cancers from the Ontario Familial Breast Cancer Registry.

ABSTRACT: Breast carcinomas, including basal and hereditary cases, often present with a prominent tumoral lymphocytic infiltrate. Chemokines could play a role in attracting these cells and contribute to tumor progression. We explored tumoral expression of CXCL10 and determined the relationship between CXCL10 and lymphocytic infiltrate in a cohort of breast cancers.Using tissue microarrays of 364 breast tumors, we evaluated expression of CXCL10 and its receptor, CXCR3, in relation to histopathologic features, biomarkers, and lymphocyte markers. In addition, we overexpressed CXCL10 and CXCR3 in MCF7 breast cancer cells and monitored T-lymphocyte migration and invasion.Forty-five percent of tumors expressed CXCL10, and a significant association was found with CXCR3 and lymphocytic infiltrate. Further characterization of the lymphocytic infiltrate revealed an association with CXCL10 expression for peritumoral CD4+ and CD8+ lymphocytes. CD8+ intratumoral lymphocytes, FOXP3+ regulatory T cells (Tregs), and T-BET+ T(H)1 cells were associated with BRCA1 and basal tumors. Conditioned media from MCF7 cells overexpressing both CXCL10 and CXCR3 increased T-lymphocyte migration and invasion.Our findings suggest that CXCL10 may act in a paracrine manner, affecting the tumor microenvironment, and in an autocrine manner, acting on the tumor cells themselves and may play a role in tumor invasiveness and progression. The CXCL10-CXCR3 axis can serve as a potential target in BRCA1 and basal breast cancers, which present with a prominent lymphocytic infiltrate and a poor prognosis. Clin Cancer Res; 19(2); 336-46. ©2012 AACR.

SUBMITTER: Mulligan AM

PROVIDER: S-EPMC3548938 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Tumoral lymphocytic infiltration and expression of the chemokine CXCL10 in breast cancers from the Ontario Familial Breast Cancer Registry.

Mulligan Anna Marie AM Raitman Irene I Feeley Linda L Pinnaduwage Dushanthi D Nguyen Linh T LT O'Malley Frances P FP Ohashi Pamela S PS Andrulis Irene L IL

Clinical cancer research : an official journal of the American Association for Cancer Research 20121204 2

<h4>Purpose</h4>Breast carcinomas, including basal and hereditary cases, often present with a prominent tumoral lymphocytic infiltrate. Chemokines could play a role in attracting these cells and contribute to tumor progression. We explored tumoral expression of CXCL10 and determined the relationship between CXCL10 and lymphocytic infiltrate in a cohort of breast cancers.<h4>Experimental design</h4>Using tissue microarrays of 364 breast tumors, we evaluated expression of CXCL10 and its receptor, ...[more]

PMID: 23213058

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Project description:Our objective was to determine whether the frequencies of non-ovarian cancers (NOC) within families in a large Familial Ovarian Cancer Registry (FOCR) are significantly different from the frequencies listed in the SEER database. The FOCR was established in 1981. Registry members are families with two or more first degree relatives who have a diagnosis of ovarian cancer, three or more cases of cancer on one side of the family with at least one being ovarian, at least one female with two or more primary cancers in which one is ovary, or a history of two or more cancers in the family with at least one being ovarian cancer diagnosed before the age of 45. The data was analyzed to find relative rates of 10 of the most common cancers found within the database, with the exception of ovarian and breast. These include bladder, CNS, cervical, colorectal, liver, lung, pancreas, prostate, stomach, and uterine. Cancers were further stratified by age at diagnosis, and compared to information in the SEER database. There are 2,671 pedigrees and a total of 50,454 individuals within the FOCR. There are 1,938 families with two or more relatives with ovarian cancer, accounting for 4,816 individuals with ovarian cancer. The total number of individuals with ovarian cancer is 5,421. Of these individuals with ovarian cancer, 2,249 have been verified with testing or physician correspondence. The frequencies of the NOCs within the registry were higher than that of the general population as described in the SEER database. In particular, the overall frequencies of cancers of the bladder, cervix, prostate, and uterus were higher within the FOCR at 2.3, 7.4, 25.2, and 11.9 per 1,000 respectively. Furthermore, diagnoses of both cervical and uterine cancers tended to occur at an earlier age within the FOCR. The overall frequencies of cancers of the bladder, cervix, prostate, and uterus are higher in the FOCR compared with a general population database. Future studies on segregation analysis and genome-wide linkage studies are warranted on families with NOC within the Familial Ovarian Cancer Registry.

Dataset Information

Tumoral lymphocytic infiltration and expression of the chemokine CXCL10 in breast cancers from the Ontario Familial Breast Cancer Registry.

Publications

Tumoral lymphocytic infiltration and expression of the chemokine CXCL10 in breast cancers from the Ontario Familial Breast Cancer Registry.

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