Search

Aims: To characterize clinico-pathological features and clinical outcome of low grade triple negative early breast carcinomas. Material and methods: Between January 2005 and December 2006, 300 tumours were classified as triple negative (ER-ve, PR-ve, HER2 0/1+) out of 3000 patients treated for a breast cancer at the Institut curie. Patients with a low-grade (grade 1 and 2 according to Ellis and Elston) T1 and small T2 (< 3cm) breast carcinoma treated with surgery first were considered in our study. Immunohistochemistry was performed with ER, PR, Androgen Receptor (AR), HER2, Ki67, EGFR, CK5/6, CK14 and CK8/18 antibodies for all tumours; GCDFP15 for invasive lobular carcinomas (ILC) and invasive ductal carcinoma (IDC) with apocrine features, and CA15-3 to assess the inverted polarity if needed. Results: We identified 36 low-grade carcinomas out of 186 triple negative breast carcinomas (19%). Thirty-two tumours were grade 2 and four tumours grade 1 and associated with a low or a moderate mitotic score. Ki67 proliferation index was high (20%) in 22 cases (61 %) (median: 22%-mean: 29%). Thirty-one (86%) tumours showed a basal-like phenotype (EGFR+ or CK5/6+ or CK14 +). Interestingly, the five "nul" (non basal-like) triple negative tumours demonstrated a low proliferation index (Ki67 20%). All but one tumors expressed CK8/18. The tumour's size varied between 3 and 37 mm (mean = 17.2). Lympho- vascular invasion was present in 10 cases (27%). High and intermediate grade ductal carcinoma in situ component was associated in 28 cases (77%). Stroma was abundant and associated with a lymphocytic infiltrate in all cases. Various histological types were observed: 16 IDC (44%), 7 ILC (19%), 5 IDC with apocrine differentiation, 2 micropapillary, 1 papillary, 1 mucinous, 3 adenoid cystic and one low grade adeno-squamous carcinomas. Three out of 16 IDC showed a week nuclear positivity with AR. Five and six out of the seven ILC were positive for AR and GCDFP15 respectively. All carcinomas with apocrine differentiation were AR and CGDFP15 positive. Conversely, all micropapillary, papillary and mucinous carcinomas were AR negative. The mean age of patients was 61.6 years. Distant metastases occurred in five patients. Thirty-three (91 %) women were alive and 29 (80%) of them without evidence of cancer at 6 years of follow-up. Conclusion: Low grade invasive carcinomas represent 19% of the cases in our series of 186 triple negative early breast carcinomas and were diagnosed in patients older than 60 years. These cases were of various histological types, were all associated with a marked lymphocytic infiltrate and in the majority of the cases with high grade ductal carcinomas in situ. Despite a low mitotic activity, proliferation index was generally higher than 20% except for "nul" non-basal cases. However, patient's overall survival seemed to be better than that reported for high grade triple negative breast cancer. Histological types, proliferation and age should be taken into account for treatment decision in triple negative early breast carcinoma patients. [ABSTRACT FROM AUTHOR]

The prognostic impact of tumor-infiltrating lymphocytes (TILs) within invasive lobular carcinoma (ILC) remains to be better characterized. In estrogen receptor (ER)-negative invasive ductal carcinomas of no special type (IDC-NST), TILs are associated with good prognosis. The aim of this study was to examine TILs in ILC, with particular focus on prognostic and clinicopathologic features. A cohort comprising 459 consecutive ILCs diagnosed in a single institution from 2005 to 2008 met the eligibility criteria for this study. The percentage of tumor area occupied by TILs was quantified by two breast pathologists and categorized into three groups: no TILs, ≤5%, >5%. Clinicopathologic features were tested by Fisher's exact tests or Chi 2 tests. Overall survival (OS) and invasive disease-free survival (iDFS) were estimated by Kaplan-Meier and Cox proportional hazard statistics. There were 239 TIL-negative cases, 185 cases with ≤5% TILs, and 35 cases with >5% TILs. TILs were associated with younger age, larger tumors, lymph node involvement, poor Nottingham prognostic index, HER2 amplification, multinucleation, and prominent nucleoli (p < 0.05). Poor OS was significantly associated with increasing TILs in the univariate Cox proportional hazards model (p < 0.001) and Kaplan-Meier estimator (p < 0.05, log-rank test). Similar results were observed for iDFS (p = 0.004 for Cox univariate and p = 0.005 for log-rank test). Notably, TILs can identify a subset of ILC patients with poor OS independently of molecular subtype and lymph node metastases (multivariate Cox, p < 0.001, OS hazard ratio (HR) = 4.38 and HR = 6.15, for ≤5% and >5% TILs, respectively, vs. absence of TILs). Prominent nucleoli was the only nuclear feature associated with poor OS (p = 0.05) and iDFS (p = 0.05) in univariate Cox survival analysis. TILs represent a promising new morphologic biomarker associated with poor outcome of ILC, in contrast with that observed in ER-negative IDC-NST.

Background: Leukotriene B4 (LTB(4) ) has chemotactic properties for activated T cells expressing the high-affinity receptor BLT(1) . This study investigated whether the LTB(4) antagonist (CP-105,693), selective for BLT(1) receptor, could protect mice from colitis mediated by specific cytotoxic CD8(+) T lymphocytes (CTL)., Methods: Virus-specific colitis was induced in C57Bl/6 mice transferred with lymphoid cells from P14 TcR Tg mice which are specific to class I GP33 peptide of LCMV. Mice were immunized with GP33-pulsed dendritic cells and colitis was elicited by intrarectal administration of the peptide. Colitis was evaluated by body weight loss and macroscopic and histological analysis of colon. In vivo priming of specific CD8(+) CTL was determined using interferon (IFN)-γ ELISPOT and in vivo CTL assays. In some experiments mice were treated with a selective LTB(4) receptor antagonist., Results: Immunization with GP33-pulsed dendritic cells (DCs) induced priming of specific CD8(+) CTL, as shown by the presence of IFN-γ-producing CD8(+) T cells in colon draining lymph nodes and in vivo CTL assays. Intrarectal challenge with GP33 induced severe colitis and recruitment of granzyme B(+) P14 CD8(+) cells in colon. Treatment with the specific LTB(4) receptor antagonist before elicitation of colitis reduced the severity of colitis and decreased the frequency of specific effectors., Conclusions: Colitis can be induced by IFN-γ-producing cytotoxic CD8(+) CTL specific for viral antigen. Blockade of the LTB(4) /BLT(1) pathway by a selective BLT(1) receptor antagonist attenuates colitis by inhibiting CD8(+) effectors recruitment in colon. These data illustrate the therapeutic potential of LTB(4) receptor selective antagonists in protection from CD8(+) T-cell-mediated intestinal inflammation., (Copyright © 2010 Crohn's & Colitis Foundation of America, Inc.)