Yong Hannah Wen

Memorial Sloan-Kettering Cancer Center, New York City, New York, United States

Are you Yong Hannah Wen?

Claim your profile

Publications (9)41.98 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Microglandular adenosis (MGA) is a lesion composed of small infiltrating glands lined by S100-positive, estrogen receptor (ER)-negative epithelial cells and lacking a myoepithelial cell layer. Although classified as a benign epithelial proliferation, there is evidence to suggest that MGA may constitute a non-obligate precursor of triple-negative breast cancer (TNBC). We sought to define the mutational landscape of MGAs and of TNBCs arising in MGA, and to determine whether MGAs may constitute the substrate from which the TNBCs originated. Design: Six cases of MGAs and three of atypical MGAs (AMGAs) associated with in situ or invasive TNBC were collected. DNA from distinct morphologic components and matched normal tissue was extracted from microdissected representative sections and subjected to massively parallel sequencing targeting all coding regions of 273 genes recurrently mutated in breast cancer or related to DNA repair. Single nucleotide variants were detected by MuTect; insertions and deletions were identified by Strelka and VarScan2. Results: MGAs (n=6) and AMGAs (n=3) consistently displayed at least one somatic mutation (range 5-17 and 1-10, respectively), whereas TNBCs (n=4) associated with MGA/AMGA harbored 6 to 11 somatic mutations. Four to 7 mutations identified in MGAs/AMGAs were also detected in their associated invasive TNBCs, and in all cases identical TP53 mutations were found in the MGA and/or AMGA and in the associated TNBC; however the latter harbored additional mutations affecting known cancer genes. In the MGAs/AMGAs lacking TP53 mutations, mutations affecting known driver genes, such as PIK3CA, ERBB3, PTEN, FGFR2 and INPP4B, were identified. Conclusions: MGA is a clonal and neoplastic lesion, harboring recurrent mutations in TP53 and other bona fide cancer genes. Identical somatic mutations were identified in MGAs/AMGAs and matched invasive TNBCs, providing evidence to suggest that these lesions may constitute non-obligate precursors of TNBCs. Category: Breast Pathology
    2015 USCAP Annual Meeting; 03/2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Microglandular adenosis (MGA) is a lesion composed of small infiltrating glands lined by S100-positive, estrogen receptor (ER)-negative epithelial cells and lacking a myoepithelial cell layer. Although classified as a benign epithelial proliferation, there is evidence to suggest that MGA may constitute a non-obligate precursor of triple-negative breast cancer (TNBC). We sought to define the mutational landscape of MGAs and of TNBCs arising in MGA, and to determine whether MGAs may constitute the substrate from which the TNBCs originated. Design: Six cases of MGAs and three of atypical MGAs (AMGAs) associated with in situ or invasive TNBC were collected. DNA from distinct morphologic components and matched normal tissue was extracted from microdissected representative sections and subjected to massively parallel sequencing targeting all coding regions of 273 genes recurrently mutated in breast cancer or related to DNA repair. Single nucleotide variants were detected by MuTect; insertions and deletions were identified by Strelka and VarScan2. Results: MGAs (n=6) and AMGAs (n=3) consistently displayed at least one somatic mutation (range 5-17 and 1-10, respectively), whereas TNBCs (n=4) associated with MGA/AMGA harbored 6 to 11 somatic mutations. Four to 7 mutations identified in MGAs/AMGAs were also detected in their associated invasive TNBCs, and in all cases identical TP53 mutations were found in the MGA and/or AMGA and in the associated TNBC; however the latter harbored additional mutations affecting known cancer genes. In the MGAs/AMGAs lacking TP53 mutations, mutations affecting known driver genes, such as PIK3CA, ERBB3, PTEN, FGFR2 and INPP4B, were identified. Conclusions: MGA is a clonal and neoplastic lesion, harboring recurrent mutations in TP53 and other bona fide cancer genes. Identical somatic mutations were identified in MGAs/AMGAs and matched invasive TNBCs, providing evidence to suggest that these lesions may constitute non-obligate precursors of TNBCs. Category: Breast Pathology
    2015 USCAP Annual Meeting; 03/2015
  • Journal of Clinical Oncology 06/2014; DOI:10.1200/JCO.2013.50.0272 · 17.88 Impact Factor
  • Dara S Ross, Yong Hannah Wen, Edi Brogi
    [Show abstract] [Hide abstract]
    ABSTRACT: Ductal carcinoma in situ (DCIS) is an established precursor of invasive breast carcinoma. Immunoperoxidase stains for selected markers can assist pathologists in the diagnosis of challenging ductal epithelial proliferations, but they cannot replace morphologic evaluation as the primary and critical assessment of this disease. Molecular studies provide further insight into how DCIS progresses to invasive carcinoma and also confirm the heterogeneity of this lesion. Morphology-based knowledge, immunohistochemistry, and molecular advances in DCIS are the subjects of this review.
    Advances in anatomic pathology 07/2013; 20(4):205-16. DOI:10.1097/PAP.0b013e3182976ed5 · 3.10 Impact Factor
  • Histopathology 04/2013; 63(3). DOI:10.1111/his.12165 · 3.30 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We previously demonstrated a high specificity of immunohistochemistry using epidermal growth factor receptor (EGFR) mutation-specific antibodies in lung adenocarcinoma and correlation with EGFR mutation analysis. In this study, we assessed EGFR mutation status by immunohistochemistry in a variety of extrapulmonary malignancies, especially those that frequently show EGFR overexpression. Tissue microarrays containing triplicate cores of breast carcinomas (n=300), colorectal carcinomas (n=65), pancreatic adenocarcinoma (n=145), and uterine carcinosarcoma or malignant mixed müllerian tumors (n=25) were included in the study. Tissue microarray of lung adenocarcinoma with known EGFR mutation status was used as reference. Immunohistochemistry was performed using antibodies specific for the E746-A750del and L858R mutations. In pulmonary adenocarcinoma, a staining intensity of 2+ or 3+ correlates with mutation status and is therefore considered as positive. Out of 300 breast carcinomas, 293 (98%) scored 0, 5 (2%) had 1+ staining, 2 (1%) were 2+ for the L858R antibody. All breast carcinomas scored 0 with the E746-A750 antibody. All the colorectal, pancreatic carcinomas and malignant mixed müllerian tumors were negative (0) for both antibodies. Molecular analysis of the breast carcinomas that scored 2+ for L858R showed no mutation. Our results show that EGFR mutation-specific antibodies could be an additional tool distinguishing primary versus metastatic carcinomas in the lung. False-positivity can be seen in breast carcinoma but is extremely rare (1%).Modern Pathology advance online publication, 19 April 2013; doi:10.1038/modpathol.2013.53.
    Modern Pathology 04/2013; DOI:10.1038/modpathol.2013.53 · 6.36 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Microglandular adenosis is a rare glandular lesion of the breast, which can mimic well-differentiated invasive carcinoma, and is characterized by a haphazard proliferation of uniform small round glands with open lumina and lacking a myoepithelial cell layer. This lesion has a rather unique immunohistochemical profile characterized by expression of cytokeratins and S-100, and lack of estrogen receptor (ER) and progesterone receptor (PR). The role of microglandular adenosis as a potential precursor of invasive breast cancer has long been a matter of controversy; however, recent molecular analyses have demonstrated that these lesions are heterogeneous at the genetic level, and that at least a subset of microglandular adenosis are clonal and display gene copy number alterations. Importantly, the pattern of genetic aberrations found in microglandular adenosis differs from that of other non-obligate precursors of ER-positive breast cancer. Carcinomas arising in microglandular adenosis are mostly of triple-negative phenotype (i.e. lack of ER, PR and HER2) and express S100, similar to microglandular adenosis. Genetic alterations found in microglandular adenosis have been shown to be similar to those found in synchronous invasive carcinomas. Here we review the clinical, morphological, and molecular features of microglandular adenosis, with an emphasis on its role as a non-obligate precursor of triple-negative breast cancer, and discuss areas for future research endeavors to clarify the clinical and biological significance of these fascinating lesions.
    Histology and histopathology 04/2013; · 2.24 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: BRCA1 germline mutation carriers usually develop ER, PR and HER2 negative breast carcinoma. Somatic BRCA1 mutations are rare in sporadic breast cancers, but other mechanisms could impair BRCA1 functions in these tumors, particularly in triple-negative breast carcinomas (TNBCs). Id4, a helix-loop-helix DNA binding factor, blocks BRCA1 gene transcription in vitro and could downregulate BRCA1 in vivo. We compared Id4 immunoreactivity in 101 TNBCs versus 113 non-TNBCs, and correlated the results with tumor morphology and immunoreactivity for CK5/6, CK14, EGFR, and androgen receptor (AR). Id4 was present in 76 out of 101 (75 %) TNBCs: 40 (40 %) TNBCs displayed Id4 positivity in >50 % of neoplastic cells, 23 (23 %) in 5-50 %, and 13 (13 %) in <5 %. In contrast, only 6 (5 %) of 113 non-TNBCs showed focal Id4 positivity, limited to fewer than 5 % of the tumor (p < 0.0001). Id4 expression significantly associated with high histologic grade (p = 0.0002) and mitotic rate (p = 0.006). Id4 decorated all 12 TNBCs with large central acellular zone of necrosis in our series, with positive staining in 10-90 % of the cells. Id4 signal strongly correlated with cytokeratin CK14 reactivity (p < 0.0001), but not with CK5/6 and EGFR. All apocrine carcinomas in our series were positive for AR and most for EGFR, but they were negative for CK5/6, CK14, and Id4, with only two exceptions. Our results document substantial expression of Id4 in most TNBCs, which could result in functional downregulation of BRCA1 pathways in these tumors.
    Breast Cancer Research and Treatment 04/2012; 135(1):93-102. DOI:10.1007/s10549-012-2070-0 · 4.20 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The authors evaluated the clinical characteristics, natural history, and outcomes of patients who had ≤1 cm, lymph node-negative, triple-negative breast cancer (TNBC). After excluding patients who had received neoadjuvant therapy, 1022 patients with TNBC who underwent definitive breast surgery during 1999 to 2006 were identified from an institutional database. In total, 194 who had lymph node-negative tumors that measured ≤1 cm comprised the study population. Clinical data were abstracted, and survival outcomes were analyzed. The median follow-up was 73 months (range, 5-143 months). The median age at diagnosis was 55.5 years (range, 27-84 years). Tumor (T) classification was microscopic (T1mic) in 16 patients (8.2%), T1a in 49 patients (25.3%), and T1b in 129 patients (66.5%). Most tumors were poorly differentiated (n = 142; 73%), lacked lymphovascular invasion (n = 170; 87.6%), and were detected by screening (n = 134; 69%). In total, 129 patients (66.5%) underwent breast-conserving surgery, and 65 patients (33.5%) underwent mastectomy. One hundred thirteen patients (58%) received adjuvant chemotherapy, and 123 patients (63%) received whole-breast radiation. The patients who received chemotherapy had more adverse clinical and disease features (younger age, T1b tumor, poor tumor grade; all P < .05). Results from testing for the breast cancer (BRCA) susceptibility gene were available for 49 women: 19 women had BRCA1 mutations, 7 women had BRCA2 mutations, and 23 women had no mutations. For the entire group, the 5-year local recurrence-free survival rate was 95%, and the 5-year distant metastasis-free survival rate was 95%. There was no difference between patients with T1mic/T1a tumors and patients with T1b tumors in the distant recurrence rate (94.5% vs 95.5%, respectively; P = .81) or in the receipt of chemotherapy (95.9% vs 94.5%, respectively; P = .63). Excellent 5-year locoregional and distant control rates were achievable in patients with TNBC who had tumors ≤1.0 cm, 58% of whom received chemotherapy. These results identified a group of patients with TNBC who had favorable outcomes after early detection and multimodality treatment. Cancer 2012. © 2012 American Cancer Society.
    Cancer 02/2012; 118(20):4944-52. DOI:10.1002/cncr.27480 · 4.90 Impact Factor