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

Diagnostic Pathology

Lars A Akslen¹  Marian D Gundersen³  Ingunn M Stefansson¹  Pål Suhrke²  Ying Chen²  Tor A Klingen² 

[1] Department of Pathology, Haukeland University Hospital, Bergen, Norway;Department of Pathology, Vestfold Hospital Trust, Tønsberg, Norway;Department of Radiology, Vestfold Hospital Trust, Tønsberg, Norway

关键词: Adverse prognostic factors;    Basal-like phenotype;    Breast cancer;    Thyroid transcription factor-1;   

Others  :  806962
DOI  :  10.1186/1746-1596-8-80

 received in 2013-03-12, accepted in 2013-04-28,  发布年份 2013

【 摘 要 】

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.

Virtual slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/8313753509421182 webcite

【 授权许可】

   
2013 Klingen et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Berghmans T, Paesmans M, Mascaux C, Martin B, Meert AP, Haller A: Thyroid transcription factor 1–a new prognostic factor in lung cancer: a meta-analysis. Ann Oncol 2006, 17(11):1673-1676.
• [2]Ordonez NG: Thyroid transcription factor-1 is a marker of lung and thyroid carcinomas. Adv Anat Pathol 2000, 7(2):123-127.
• [3]Wong NA, Kamel H, Sheffield EA, Sohail M: Positive immunostaining for thyroid transcription factor-1 in colorectal adenocarcinoma using the 8G7G3/1 monoclonal antibody. J Clin Pathol 2008, 61(9):1070-1071.
• [4]Kubba LA, McCluggage WG, Liu J, Malpica A, Euscher ED, Silva EG: Thyroid transcription factor-1 expression in ovarian epithelial neoplasms. Mod Pathol 2008, 21(4):485-490.
• [5]Siami K, McCluggage WG, Ordonez NG, Euscher ED, Malpica A, Sneige N: Thyroid transcription factor-1 expression in endometrial and endocervical adenocarcinomas. Am J Surg Pathol 2007, 31(11):1759-1763.
• [6]Bejarano PA, Baughman RP, Biddinger PW, Miller MA, Fenoglio-Preiser C: al-Kafaji B, et al. Surfactant proteins and thyroid transcription factor-1 in pulmonary and breast carcinomas. Mod Pathol 1996, 9(4):445-452.
• [7]Robens J, Goldstein L, Gown AM, Schnitt SJ: Thyroid transcription factor-1 expression in breast carcinomas. Am J Surg Pathol 2010, 34(12):1881-1885.
• [8]Sakurai A, Sakai Y, Yatabe Y: Thyroid transcription factor-1 expression in rare cases of mammary ductal carcinoma. Histopathology 2011, 59(1):145-148.
• [9]Klingen TA, Chen Y, Gundersen MD, Aas H, Westre B, Sauer T: Thyroid transcription factor-1 positive primary breast cancer: a case report with review of the literature. Diagn Pathol 2010, 5:37. BioMed Central Full Text
• [10]Ersahin C, Bandyopadhyay S, Bhargava R: Thyroid transcription factor-1 and “basal marker”–expressing small cell carcinoma of the breast. Int J Surg Pathol 2009, 17(5):368-372.
• [11]Christie M, Chin-Lenn L, Watts MM, Tsui AE, Buchanan MR: Primary small cell carcinoma of the breast with TTF-1 and neuroendocrine marker expressing carcinoma in situ. Int J Clin Exp Pathol 2010, 3(6):629-633.
• [12]Straume O, Akslen LA: Alterations and prognostic significance of p16 and p53 protein expression in subgroups of cutaneous melanoma. Int J Cancer 1997, 74(5):535-539.
• [13]Elston CW, Ellis IO: Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. C. W. Elston & I. O. Ellis. Histopathology 1991, 19:403-410. Histopathology 2002 Sep;41(3A):151-2, discussion
• [14]Mannelqvist M, Stefansson I, Salvesen HB, Akslen LA: Importance of tumour cell invasion in blood and lymphatic vasculature among patients with endometrial carcinoma. Histopathology 2009, 54(2):174-183.
• [15]Collett K, Stefansson IM, Eide J, Braaten A, Wang H, Eide GE: A basal epithelial phenotype is more frequent in interval breast cancers compared with screen detected tumors. Cancer Epidemiol Biomarkers Prev 2005, 14(5):1108-1112.
• [16]Bisceglia M, Galliani C, Rosai J: TTF-1 expression in breast carcinoma-the chosen clone matters. Am J Surg Pathol 2011, 35(7):1087-1088.
• [17]Matoso A, Singh K, Jacob R, Greaves WO, Tavares R, Noble L: Comparison of thyroid transcription factor-1 expression by 2 monoclonal antibodies in pulmonary and nonpulmonary primary tumors. Appl Immunohistochem Mol Morphol 2010, 18(2):142-149.
• [18]Comperat E, Zhang F, Perrotin C, Molina T, Magdeleinat P, Marmey B: Variable sensitivity and specificity of TTF-1 antibodies in lung metastatic adenocarcinoma of colorectal origin. Mod Pathol 2005, 18(10):1371-1376.
• [19]Nordiqc. 2012. http://www.nordiqc.org/Run-33-B12-G2/Assessment/assessment-33-TTF1.htm webcite
• [20]Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA: Molecular portraits of human breast tumours. Nature 2000, 406(6797):747-752.
• [21]Reis-Filho JS, Tutt AN: Triple negative tumours: a critical review. Histopathology 2008, 52(1):108-118.
• [22]Cakir A, Gonul II, Uluoglu O: A comprehensive morphological study for basal-like breast carcinomas with comparison to nonbasal-like carcinomas. Diagn Pathol 2012, 7:145. BioMed Central Full Text
• [23]Arnes JB, Brunet JS, Stefansson I, Begin LR, Wong N, Chappuis PO: Placental cadherin and the basal epithelial phenotype of BRCA1-related breast cancer. Clin Cancer Res 2005, 11(11):4003-4011.
• [24]Nielsen TO, Hsu FD, Jensen K, Cheang M, Karaca G, Hu Z: Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res 2004, 10(16):5367-5374.
• [25]Hajdu SI, Urban JA: Cancers metastatic to the breast. Cancer 1972, 29(6):1691-1696.
• [26]Georgiannos SN, Chin J, Goode AW, Sheaff M: Secondary neoplasms of the breast: a survey of the 20th Century. Cancer 2001, 92(9):2259-2266.
• [27]Vergier B, Trojani M, de Mascarel I, Coindre JM, Le Treut A: Metastases to the breast: differential diagnosis from primary breast carcinoma. J Surg Oncol 1991, 48(2):112-116.
• [28]Klingen TA, Klaasen H, Aas H, Chen Y, Akslen LA: Secondary breast cancer: a 5-year population-based study with review of the literature. APMIS 2009, 117(10):762-767.
• [29]Ishibashi H, Suzuki T, Suzuki S, Niikawa H, Lu L, Miki Y: Progesterone receptor in non-small cell lung cancer–a potent prognostic factor and possible target for endocrine therapy. Cancer Res 2005, 65(14):6450-6458.
• [30]Nose N, Uramoto H, Iwata T, Hanagiri T, Yasumoto K: Expression of estrogen receptor beta predicts a clinical response and longer progression-free survival after treatment with EGFR-TKI for adenocarcinoma of the lung. Lung Cancer 2011, 71(3):350-355.
• [31]Takeda Y, Tsuta K, Shibuki Y, Hoshino T, Tochigi N, Maeshima AM: Analysis of expression patterns of breast cancer-specific markers (mammaglobin and gross cystic disease fluid protein 15) in lung and pleural tumors. Arch Pathol Lab Med 2008, 132(2):239-243.
• [32]Wang LJ, Greaves WO, Sabo E, Noble L, Tavares R, Ng T: GCDFP-15 positive and TTF-1 negative primary lung neoplasms: a tissue microarray study of 381 primary lung tumors. Appl Immunohistochem Mol Morphol 2009, 17(6):505-511.
• [33]Ye J, Findeis-Hosey JJ, Yang Q, McMahon LA, Yao JL, Li F: Combination of napsin A and TTF-1 immunohistochemistry helps in differentiating primary lung adenocarcinoma from metastatic carcinoma in the lung. Appl Immunohistochem Mol Morphol 2011, 19(4):313-317.