Clinicopathologic and Prognostic Significance of Transducin-Like Enhancer of Split 1 Protein Expression in Invasive Breast Cancer / 한국유방암학회지

PURPOSE: Transducin-like enhancer of split 1 (TLE1) is a member of the TLE family of transcriptional co-repressors that control the transcription of a wide range of genes. We investigated the prognostic significance of TLE1 protein expression in breast cancers by using immunohistochemistry and explored the relationship of TLE1 with clinicopathological parameters. METHODS: Immunohistochemistry was performed on 456 cases of breast cancer tiled on tissue microarrays. The relationship between TLE1 expression in normal breast specimens and ductal carcinoma in situ (DCIS) was also analyzed. RESULTS: TLE1 was highly expressed in 57 of 456 (12.5%) carcinoma samples. TLE1 was more frequently expressed in DCIS and invasive breast cancers than in normal breast tissue (p=0.002). High expression of TLE1 significantly correlated with negative lymph node (LN) metastasis (p=0.007), high histologic grade (p<0.001), estrogen receptor negativity (p<0.001), progesterone receptor negativity (p<0.001), human epidermal growth factor receptor 2 (HER2) positivity (p<0.001), and high Ki-67 proliferation index (p<0.001). Based on intrinsic subtypes, high TLE1 expression was strongly associated with HER2+ and triple-negative breast cancers (TNBC) (p<0.001). Survival analysis demonstrated no significant association between TLE1 expression and disease-free survival (DFS) (p=0.167) or overall survival (OS) (p=0.286). In subgroup analyses, no correlation was found between TLE1 expression and DFS or OS according to LN status or intrinsic subtype. CONCLUSION: High TLE1 expression is significantly associated with the HER2+ and TNBC subtypes. This is the first study documenting immunohistochemical expression of TLE1 in invasive breast cancer and its association with clinicopathological parameters, prognosis, and intrinsic subtype.

Prognostic and Clinicopathological Significance of Transducer-Like Enhancer of Split 1 Expression in Gastric Cancer

PURPOSE: Transducer-like enhancer of split 1 (TLE1) is a member of the Groucho/TLE family of transcriptional co-repressors that regulate the transcriptional activity of numerous genes. TLE1 is involved in the tumorigenesis of various tumors. We investigated the prognostic significance of TLE1 expression and its association with clinicopathological parameters in gastric cancer (GC) patients. MATERIALS AND METHODS: Immunohistochemical analysis of six tissue microarrays was performed to examine TLE1 expression using 291 surgically resected GC specimens from the Soonchunhyang University Cheonan Hospital between July 2006 and December 2009. RESULTS: In the non-neoplastic gastric mucosa, TLE1 expression was negative. In GC, 121 patients (41.6%) were positive for TLE1. The expression of TLE1 was significantly associated with male gender (P=0.021), less frequent lymphatic (P=0.017) or perineural invasion (P=0.029), intestinal type according to the Lauren classification (P=0.024), good histologic grade (P<0.001), early pathologic T-stage (P=0.012), and early American Joint Committee on Cancer stage (P=0.022). In the Kaplan-Meier analysis, the TLE1 expression was significantly associated with longer disease-free (P=0.022) and overall (P=0.001) survival rates. CONCLUSIONS: We suggested that TLE1 expression is a good prognostic indicator in GCs.

Immunohistochemical validation of TLE1, a novel marker, for synovial sarcomas.

Background & objectives: Logistic and financial constraints limit application of several available immunohistochemical (IHC) markers and molecular analysis in every case of synovial sarcoma, diagnosed in our settings. Recently, TLE1 has been recognized as a robust IHC marker for diagnosing a synovial sarcoma. Here, we present IHC features of synovial sarcomas, including TLE1 expression in these cases and in some other tumours. Methods: Conventional sections from 42 synovial sarcomas (30 retrospective & 12 prospectively diagnosed) were subjected to TLE1 IHC staining, including 21 tumours confirmed with molecular testing. TLE1 immunostaining was graded from 0, 1+, 2+, 3+, with 2+ or 3+ grades interpreted as positive staining. Results: Of the 42 tumours, 26 (61.9%) were of monophasic spindle cell type, 13 biphasic type (30.9%), two (4.7%) calcifying type and remaining one (2.3%) was a poorly differentiated synovial sarcoma. On immunohistochemistry (IHC), tumours were positive for epithelial membrane antigen (EMA) (26/34, 76.4%), cytokeratin (CK)7 (6/10, 60%), CK/MNF116 (6/21, 28.6%), B cell lymphoma 2 (BCL2) (36/37, 97.3%), cluster of differentiation molecule 99 (MIC2) (23/31, 74.1%) and transducin-like enhancer of split 1 (TLE1) (40/42, 95.2%), while negative for CD34 in all 21 tumours, wherever performed. TLE1 was also positive in tumour controls, including schwannomas (5/5, 100%), neurofibromas (2/2, 100%), malignant peripheral nerve sheath tumors (2/12, 17%) and Ewing sarcomas (4/10, 40%). TLE1 sensitivity for diagnosis of synovial sarcomas was 95.2 per cent. Its overall specificity was 63.7 per cent, whereas with regards to tumors forming its closest differential diagnoses, its specificity was 72 per cent. Interpretation & conclusions: Although molecular confirmation is the diagnostic gold standard for synovial sarcoma, TLE1, in view of its high sensitivity may be a useful marker within the optimal IHC panel comprising EMA, BCL2, MIC2, CD34 and CK7, especially on small biopsy samples, for substantiating a diagnosis of synovial sarcoma. Awareness of TLE1 expression in other tumours and its correct interpretation are necessary.