Keratin 15, transcobalamin I and homeobox gene Hox-B13 expression in breast phyllodes tumors: novel markers in biological classification

Chong, Luke; Cheok, Poh Yian; Tan, Wai Jin; Thike, Aye Aye; Allen, George E.; Ang, Mei Kim; Ooi, Aik Seng; Tan, Patrick; Teh, Bin Tean; Tan, Puay Hoon

doi:10.1007/s10549-011-1555-6

Cited by 33 publications

(40 citation statements)

References 29 publications

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“…Furthermore, it has been well elucidated the associations between high serum levels of vitamin B12 and malignant hematological diseases such as chronic myeloid leukemia and acute leukemia and the pathogenesis involves release of TCN1 by proliferating granulocytes 36, 37, 40. In addition, upregulation of TCN1 both in plasm and tumor tissue have been reported in a number of solid neoplasms including HCC, salivary gland tumors, cancers of the breast, kidney, lung and stomach, and endocervical adenocarcinoma 15, 17-24, 41. Previous studies have suggested that increased serum level and expression of TCN1 in patients with HCC or secondary liver metastasis might be due to a diminished clearance of TCN1 in the liver 38, 42.…”

Section: Discussionmentioning

confidence: 99%

“…As we know, vitamin B12 plays an important role in maintenance of nervous system function, hematopoiesis, and cell metabolism 14-16. TCN1 carries vitamin B12 as it passes through the stomach and enzymatically releases it in the duodenum where it is subsequently bound by intrinsic factor (IF) 15, 17, 18. Interestingly, TCN1 has been reported to be overexpressed in some malignancies such as hepatocellular carcinoma (HCC) and cancers of the breast, lung and stomach 15, 17-24.…”

Section: Introductionmentioning

confidence: 99%

“…TCN1 carries vitamin B12 as it passes through the stomach and enzymatically releases it in the duodenum where it is subsequently bound by intrinsic factor (IF) 15, 17, 18. Interestingly, TCN1 has been reported to be overexpressed in some malignancies such as hepatocellular carcinoma (HCC) and cancers of the breast, lung and stomach 15, 17-24. Recently, a bioinformatics -based study has suggested that TCN1 as an important oncogene for the classification of normal and CRC tissues 25.…”

Section: Introductionmentioning

confidence: 99%

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Overexpression of Transcobalamin 1 is an Independent Negative Prognosticator in Rectal Cancers Receiving Concurrent Chemoradiotherapy

Lee¹,

Wei²,

Tian³

et al. 2017

J. Cancer

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Objective: Neoadjuvant concurrent chemoradiotherapy (CCRT) is an increasingly common therapeutic strategy for locally advanced rectal cancer, but stratification of risk and final outcomes remain a major challenge. Transcobalamin 1 (TCN1), a vitamin B12 (cobalamin)-binding protein, regulates cobalamin homeostasis. High expression of TCN1 have been reported in neoplasms such as breast cancer and hepatocellular carcinoma. However, little is known about the relevance of TCN1 to rectal cancer receiving CCRT. This study examined the predictive and prognostic impact of TCN1 expression in patients with rectal cancer following neoadjuvant CCRT.Methods: Through data mining from a published transcriptome of rectal cancers (GSE35452), we identified upregulation of TCN1 gene as the most significantly predicted poor response to CCRT among ion transport-related genes (GO:0006811). We evaluated TCN1 immunohistochemistry and performed an H-score analysis on endoscopic biopsy specimens from 172 rectal cancer patients receiving neoadjuvant CCRT followed by curative surgery. Expression levels of TCN1 were further correlated with clinicopathologic features, therapeutic response, tumor regression grade (TRG) and survivals including metastasis-free survival (MeFS), disease-specific survival (DSS) and recurrent-free survival (LRFS).Results: TCN1 overexpression was significantly related to advanced post-treatment tumor (T3, T4; p<0.001) and nodal status (N1, N2; p<0.001), vascular invasion (p=0.003) and inferior tumor regression grade (p < 0.001). In survival analyses, TCN1 overexpression was significantly associated with shorter DSS (p<0.0001), MeFS (p=0.0002) and LRFS (p=0.0001). Furthermore, it remained an independent prognosticator of worse DSS (p=0.002, hazard ratio=3.344), MeFS (p=0.021, hazard ratio=3.015) and LRFS (p=0.037, hazard ratio=3.037) in the multivariate comparison.Conclusion: Overexpression of TCN1 is associated with poor therapeutic response and adverse outcomes in rectal cancer patients receiving CCRT, justifying the potential prognostic value of TCN1 in rectal cancer receiving CCRT.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Overexpression of Transcobalamin 1 is an Independent Negative Prognosticator in Rectal Cancers Receiving Concurrent Chemoradiotherapy

Lee¹,

Wei²,

Tian³

et al. 2017

J. Cancer

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“…PT account for <1% of all primary breast neoplasms, although in Asian countries, they appear to be more frequently encountered,1 with a reported younger age of occurrence 7. Classification into benign, borderline and malignant categories is based on a constellation of histological parameters that primarily focuses on stromal features of atypia, mitoses, cellularity, overgrowth and nature of tumour margins 1 2 8 9. The attention on stromal features is premised on the view that the stroma of PT represents the neoplastic component that progresses and which is responsible for clinical behaviour 10–16.…”

Section: Introductionmentioning

confidence: 99%

“…Apart from many reports of biological and genetic markers that can assist in categorising or grading PT for prognostic purposes,8 9 19–30 classification of this group of tumours remains problematic in terms of standardised universal application. How the assessment of each histological parameter combines together to assign a specific grade, and whether there are histological features that are individually more important in predicting recurrent behaviour, have not been resolved 1 31–36.…”

Section: Introductionmentioning

confidence: 99%

Predicting clinical behaviour of breast phyllodes tumours: a nomogram based on histological criteria and surgical margins

li¹

2011

J Clin Pathol

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253

204

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Ubiquitin carboxy-terminal hydrolase L1 may be involved in the development of mammary phyllodes tumors

et al. 2013

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Phyllodes tumors (PTs) are characterized by co-proliferation of the stroma and epithelium, with the stroma being the neoplastic element. Ubiquitin carboxy-terminal hydrolase L1 (UCHL1) is a deubiquitinating enzyme that was originally considered to be a neuronal-specific marker, but later reports have shown both tumorigenic and antitumorigenic roles for UCHL1. Although a role for UCHL1 has been explored in many cancers, a study on PTs has never been reported. We assessed UCHL1 expression in 49 cases of PTs and 16 fibroadenomas using immunohistochemistry and examined associations with clinicopathological features. In normal breast, strong staining for UCHL1 was consistently observed in the nerve bundles, if present, in breast stroma. Scattered stromal cells showed negative to weak staining. The ductal and lobular units, in contrast, showed no staining. In contrast to the 16 fibroadenomas, of which only 3 showed mild staining, UCHL1 expression was consistently observed in all 49 PTs. There was a significantly increasing trend of UCHL1 expression with increasing PT grade (P < 0.001); strong staining was observed in 24 % of benign PTs, but was present in 56 and 90 % of borderline and malignant PTs, respectively. Consistently, UCHL1 was focally positive in regions of benign to borderline malignancy, but strongly and diffusely immunoreactive in regions of malignancy in cases of malignant PTs. In addition to PT grade, UCHL1 expression correlated with increasing stromal atypia (P = 0.01), but not with other clinicopathological parameters. In conclusion, the consistent expression of UCHL1 in PTs and an increasing trend of UCHL1 expression with an increasing PT grade suggest a role for UCHL1 in the pathogenesis and malignant progression of PTs.

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Keratin 15, transcobalamin I and homeobox gene Hox-B13 expression in breast phyllodes tumors: novel markers in biological classification

Cited by 33 publications

References 29 publications

Overexpression of Transcobalamin 1 is an Independent Negative Prognosticator in Rectal Cancers Receiving Concurrent Chemoradiotherapy

Overexpression of Transcobalamin 1 is an Independent Negative Prognosticator in Rectal Cancers Receiving Concurrent Chemoradiotherapy

Predicting clinical behaviour of breast phyllodes tumours: a nomogram based on histological criteria and surgical margins

Ubiquitin carboxy-terminal hydrolase L1 may be involved in the development of mammary phyllodes tumors

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