PTTG mRNA expression in primary breast cancer: a prognostic marker for lymph node invasion and tumor recurrence

Solbach, Christine; Roller, Marc; Fellbaum, Christian; Nicoletti, Maria Ines; Kaufmann, M.

doi:10.1016/j.breast.2003.09.008

Cited by 109 publications

(103 citation statements)

References 6 publications

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“…12,36 Aneuploidy is a common feature of tumours overexpressing PTTG, and in breast cancer, the largest number of securin-positive cells was found in the tumours with the highest degree of pleomorphism. 6,16 We also found securin expression preferentially in pleomorphic melanoma cells with highly atypical or multiple nuclei. We studied the ploidy status in relation to hPTTG1 overexpression using a series of melanomas that had been karyotyped, and observed a significantly higher number of securinpositive cells in aneuploid cases.…”

Section: Discussionmentioning

confidence: 52%

“…18 These data are in line with studies on breast, colorectal and thyroid carcinomas in which overexpression of PTTG is associated with early recurrence, or metastatic spread and thus with a poor prognosis. 8,15,16 In normal cells, the securin protein is expressed in a cell-cycle-dependent manner and regulates sister chromatid separation to opposite poles of the cell during anaphase. 4 Following cytoplasmic to nuclear translocation, it peaks in the G2/M phase and subsequently is ubiquitinated and degraded in the proteasome.…”

Section: Discussionmentioning

confidence: 99%

“…In tumours of the thyroid, securin is a prognostic marker for recurrence, 15 and in breast cancer, the extent of securin expression is associated with the presence of metastatic spread and lymph node invasion. 6,16 In cancer of the oesophagus and colorectum, high levels of hPTTG1 expression correlate with tumour invasiveness. 9 Recently, hPTTG1 has been identified as a key signature gene, with high expression predicting metastases in multiple tumour types.…”

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confidence: 99%

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Expression and possible role of hPTTG1/securin in cutaneous malignant melanoma

et al. 2006

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Human pituitary tumour-transforming gene 1 or hPTTG1 is a proto-oncogene that codes for securin, a protein involved in sister chromatid separation. Based on previous microarray data, we studied the expression of hPTTG1/securin in melanocytic lesions. In contrast to nevi and radial growth phase melanomas, securin was expressed by scattered cells in the vertical growth phase, suggesting a role in tumour progression. In a series of 29 nodular and 29 superficial spreading melanomas, matched for all histological prognostic parameters, securin expression was significantly correlated with the nodular subtype (P ¼ 0.018) and not related to thickness. In other cancers, hPTTG1 is involved in various oncogenic pathways, including induction of neovascularisation and aneuploidy, and inhibition of p53 activity. We found coexpression of securin with wildtype p53 in the same neoplastic cells in a minority of melanomas. Expression of securin was significantly correlated with the extent of aneuploidy but not with basic fibroblast growth factor immunoreactivity or microvessel density. DNA cytometry revealed that nuclei-overexpressing securin frequently showed tetraploidy or aneuploidy. Our data show that hPTTG1 is frequently overexpressed in nodular melanoma, and suggest that hPTTG1 may act as an oncogene in the vertical growth phase, either by inhibiting anaphase, thereby causing aneuploidy and genomic instability, or by modulating the function of p53, thereby impairing apoptosis.

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Section: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Expression and possible role of hPTTG1/securin in cutaneous malignant melanoma

et al. 2006

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“…This study confirms and extends our own work and that of others on the utility of securin as a marker of lymph node invasion and metastasis in solid tumors. [12][13][14]35 This is the first study describing the immunohistochemical analysis of securin expression in a large series of tumors and confirming its use as a technique that could potentially be employed in the clinical setting. Securin represents a potential novel marker of breast cancer proliferation and analysis of breast cancer securin expression may provide important prognostic insights and portend response to treatment in breast cancer.…”

Section: Securin Overexpression In Breast Cancermentioning

confidence: 54%

Securin is overexpressed in breast cancer

et al. 2005

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Securin regulates sister chromatid separation during mitosis, induces bFGF-mediated angiogenesis, and securin overexpression causes in vitro transformation and in vivo tumor formation in nude mice. As estrogen administration to oophorectomized rats increased pituitary securin expression, we used immunohistochemistry to examine securin and estrogen receptor alpha (ER-a) expression in 90 breast tumors and 18 normal breast tissues. Breast tumor securin and ER-a expression were quantitated by image analysis and expressed as fold difference relative to securin expression in normal breast tissue. Low cytoplasmic securin expression was seen in the normal breast epithelium, whereas abundant cytoplasmic and nuclear securin expression was demonstrated in all 90 breast tumors. Highest securin expression was seen in brain metastatic breast tumors (4.3-fold, Po0.01), cells derived from metastatic breast cancers (6.5-fold, Po0.001), and in invasive ductal carcinoma (mean7s.e.: 3.8-fold, Po0.001). Highly pleomorphic (4.1-fold) or highly proliferative breast tumors (1.6-fold) exhibited high immunohistochemical securin expression compared to low-grade breast tumors (Po0.05). Northern blot analysis in 12 of the breast tumors confirmed the immunohistochemical findings demonstrating increased securin mRNA expression compared to normal breast mucosa (2.5-fold, P ¼ 0.03), with highest securin evident in invasive (3.5-fold) vs noninvasive tumors (1.9-fold, P ¼ 0.03). In addition, some tumors that exhibited high securin expression also expressed high ER-a levels (Po0.0001). These results demonstrate that the estrogen-induced transforming gene, securin is abundantly expressed in breast carcinoma, and is associated with the presence of metastatic spread, and lymph node invasion. We propose immunohistochemical tumor securin expression as a potential invasive marker, and novel therapeutic target in breast cancer. Modern Pathology (2005) 18, 985-990.

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“…Overexpression of PTTG1 enhances the cell proliferation, migration, invasion, and/or tumorigenicity and the induction of aneuploidy of cells derived from cancers of the human pituitary, kidney, esophagus, breast, head, and neck, liver, thyroid, lung, etc (Solbach et al, 2004;Zhou et al, 2005;Kim et al, 2006;Malik and Kakar, 2006;Rehfeld et al, 2006;Solbach et al, 2006;Wuttig et al, 2009;Liang et al, 2011). PTTG1 overexpression correlates with metastasis and poor overall survival in various human cancers (Heaney et al, 2000;Malik and Kakar, 2006;Wuttig et al, 2009), and decreasing PTTG expression through PTTG siRNA inhibits tumor growth in ovarian (El-Naggar et al, 2007), hepatic (Cho-Rok et al, 2006).…”

Section: 3083 Pituitary Tumor Transforming Gene 1 Is An Independent mentioning

confidence: 99%