Thyroid transcription factor-1 positive primary breast cancer: a case report with review of the literature

This case describes an infiltrating breast tumour with thyroid transcription factor-1 (TTF-1) positive staining and ductal differentiation in a 72-year-old woman. The presence of ductal carcinoma in situ with positive TTF-1 is a strong indication that this is a primary tumour and not a metastasis from lung. On PET scan and CT follow up there were no other tumours found in this patient. We are not aware of any previously reported TTF-1 positive primary breast carcinoma with ductal differentiation

Expression of thyroid transcription factor-1 is associated with a basal-like phenotype in breast carcinomas

Background: The differential diagnosis between primary and secondary breast cancers might be difficult, especially in poorly differentiated tumors. Thyroid Transcription Factor-1 (TTF-1) has been regarded as a reliable marker for lung or thyroid origin, with only occasional positive staining in other tumors. However, positive cases have recently been reported among primary breast carcinomas. Methods and results: Here, we analyzed expression of TTF-1 protein (clone SPT24) by immunohistochemical staining of sections from paraffin embedded tumor samples in 247 primary breast cancers from the population- based Norwegian Breast Cancer Screening Program. Positive staining (weak or strong) was observed in 7 cases (2,8%). As novel observations, positivity was demonstrated more frequently in estrogen receptor negative cases (14,0% vs. 1,4%; p = 0,004), highly proliferative tumors (8,8% vs. 1,1%; p = 0,008), tumors with a basal-like phenotype by showing expression of CK5/6 and/or P-cadherin (11,1% vs. 1,4%; p = 0,01), and tumors with blood vessel invasion (9,7% vs. 1,9%; p = 0,04). Also, TTF-1 was associated with histological grade 3 tumors compared with grade 1 or 2 tumors (7,7% vs. 1,5%; p = 0,04) as well as lymph node positive cases (5,2% vs. 1,8%; p = 0,03). Conclusions: Our population-based findings indicate that TTF-1 may be positive in approximately 3% of primary breast cancers, and positivity indicates an association with adverse prognostic factors

Tumor-associated macrophages are strongly related to vascular invasion, non-luminal subtypes, and interval breast cancer

Tumor-associated macrophages (TAM) resemble M2 macrophages, promote tumor invasion and show strong expression of CD163 in breast cancer. We here investigated the association between CD163-positive macrophages and vascular invasion, molecular subgroups, mode of detection, and patient outcome. We performed a population-based, retrospective study of invasive breast cancer from the Norwegian Breast Cancer Screening Programme in Vestfold County (2004–2009), including 200 screen-detected and 82 interval cancers. Immunohistochemically CD163-positive macrophages were counted in the most active areas (hotspots) and dichotomized as high (upper quartile) and low counts. Lymphatic vessel involvement (LVI) and blood vessel invasion (BVI) were recorded separately based on immunohistochemical staining (D2–40 and CD31 antibodies). High levels of CD163-positive macrophages were associated with BVI and lymphatic involvement as well as interval cancer detection when compared to screening-detected tumors. In addition, the presence of high CD163+ TAM levels was more often observed in HER2-positive, basal-like and Triple-negative breast cancers and was associated with several features of aggressive tumors. In survival analyses, cases with combined high CD163 counts and BVI showed a significantly reduced recurrence-free survival (RFS) and disease-specific survival (DSS) (P < .001 for both) compared with all other cases. The presence of CD163-positive, tumor-associated macrophages is strongly related to aggressive features of breast cancer such as vessel invasion, detection between screening intervals, non-luminal molecular subgroups and reduced survival

Thyroid transcription factor-1 positive primary breast cancer: a case report with review of the literature

Abstract This case describes an infiltrating breast tumour with thyroid transcription factor-1 (TTF-1) positive staining and ductal differentiation in a 72-year-old woman. The presence of ductal carcinoma in situ with positive TTF-1 is a strong indication that this is a primary tumour and not a metastasis from lung. On PET scan and CT follow up there were no other tumours found in this patient. We are not aware of any previously reported TTF-1 positive primary breast carcinoma with ductal differentiation.</p

Breast cancer stromal elastosis is associated with mammography screening detection, low Ki67 expression and favourable prognosis in a population-based study

Background: Mammography screen-detected breast cancers have a better prognosis than predicted from established prognostic markers. A search for additional features that are characteristic for these tumours and their prognosis is needed to reduce overtreatment, a recognized challenge in breast cancer patient management today. Here, we have investigated the occurrence and importance of tumour elastosis. Methods: We performed a population based retrospective study of breast cancers detected in the Norwegian Breast Cancer Screening Programme in Vestfold County during 2004–2009. In total, 197 invasive screen-detected cancers and 75 interval cancers in patients aged 50–69 years were compared with regard to standard clinico-pathological parameters and tumour shape, as well as ER, PR, HER2 and Ki67 expression. In particular, the presence of elastotic material in tumours was graded on a 4-tiered scale (score 0–3). Results: Screen-detected cancers had a significantly higher content of stromal elastosis than interval cancers (p < 0.001). High content of elastosis (score 3) correlated strongly with stellate tumour shape, low histological grade, and ER+/HER2- status. Further, high elastosis score was significantly associated with lower Ki67 expression. In survival analyses, cases with high elastosis demonstrated increased recurrence free (p = 0.03) and disease-specific survival (p = 0.11) compared to cases with low elastosis. Conclusion: There is a strong correlation between the presence of tumour elastosis, stellate tumour shape and mammography detection of breast cancers. To our knowledge, this is the first time elastosis has been studied in relation to breast cancer detection method. Presence of elastosis is associated with low tumour cell proliferation (Ki67) and a good prognosis

Evaluation of Tumor Cell Proliferation by Ki-67 Expression and Mitotic Count in Lymph Node Metastases from Breast Cancer.

Few studies have addressed the risk of recurrence by assessing proliferation markers in lymph node metastasis from breast cancer. Here, we aimed to examine Ki-67 expression and mitotic count in lymph nodes in comparison with primary tumors. A cohort of node positive breast cancer (n = 168) was studied as a part of the prospective Norwegian Breast Cancer Screening Program (1996-2009). The percentage of Ki-67 positivity was counted per 500 tumor cells in hot-spot areas (x630). Mitotic count was conducted in the most cellular and mitotic active areas in 10 high power fields (x400). Our results showed that Ki-67 and mitotic count were significantly correlated between primary tumor and lymph nodes (Spearman`s correlation 0. 56 and 0.46, respectively) and were associated with most of the histologic features of the primary tumor. Univariate survival analysis (log-rank test) showed that high Ki-67 and mitotic count in the primary tumor and lymph node metastasis significantly predicted risk of recurrence. In multivariate analysis, mitotic count in the lymph node metastasis was an independent predictor of tumor recurrence. In conclusion, proliferation markers in lymph node metastases significantly predicted disease free survival in node positive breast cancer