Shift from cytoplasmic to nuclear maspin expression correlates with shorter overall survival in node-negative colorectal cancer

Märkl, Bruno; Arnholdt, H.; Jähnig, Hendrik; Schenkirsch, Gerhard; Herrmann, Robert A.; Haude, Karlheinz; Spatz, Hanno; Anthuber, Matthias; Schlimok, G.; Oruzio, Daniel

doi:10.1016/j.humpath.2009.10.021

Cited by 22 publications

(31 citation statements)

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“…Multivariate analysis showed that nuclear-only expression pattern is an independent predictor of improved patient survival [17,28]. However, nuclear staining was reported to be associated with a shorter overall survival in patients with node-negative colorectal cancers [16]. In the present study, we demonstrate that adenocarcinomas of the bile duct more frequently show a combined nuclear/cytoplasmic maspin immunostaining pattern in comparison…”

Section: Accepted Manuscriptsupporting

confidence: 45%

“…Maspin may function differently in different tumor types because both overexpression and downregulation have been reported in cacners of various organs [5][6][7][8][9][10][11][12][13][14][15]. A few studies have also shown that maspin expression is a useful prognostic factor for cancers [7,8,[16][17][18]. Recently, the biological functions of maspin have been linked to its subcellular localization [3,4].…”

Section: Introductionmentioning

confidence: 99%

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Diagnostic value of maspin in distinguishing adenocarcinoma from benign biliary epithelium on endoscopic bile duct biopsy

Chen

Huang

Himmelfarb³

et al. 2015

Human Pathology

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Section: Accepted Manuscriptsupporting

confidence: 45%

Section: Introductionmentioning

confidence: 99%

Diagnostic value of maspin in distinguishing adenocarcinoma from benign biliary epithelium on endoscopic bile duct biopsy

Chen

Huang

Himmelfarb³

et al. 2015

Human Pathology

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“…This suggests that high-nuclear Maspin staining is the major variable determining the association with early recurrence. This is in line with earlier reports (Dietmaier et al , 2006; Markl et al , 2010). In contrast to the results presented here, a previous study failed to detect a significant association of nuclear or cytoplasmic Maspin staining with outcome in a large cohort of stage III CRC patients (Fung et al , 2010).…”

Section: Discussionsupporting

confidence: 94%

“…Mixed-stage studies in CRC have failed to reach consensus whether Maspin is associated with good or poor prognosis (Song et al , 2002; Bettstetter et al , 2005; Markl et al , 2010). A study in patients with only stage III disease has shown that high nuclear Maspin is significantly correlated with poor overall survival (Dietmaier et al , 2006), which is in line with the results presented in this report.…”

Section: Discussionmentioning

confidence: 99%

Maspin is a marker for early recurrence in primary stage III and IV colorectal cancer

et al. 2013

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Background:Little is known about the factors that drive metastasis formation in colorectal cancer (CRC). Here, we set out to identify genes and proteins in patients with colorectal liver metastases that correlate with early disease recurrence. Such factors may predict a propensity for metastasis in earlier stages of CRC.Methods:Gene expression profiling and proteomics were used to identify differentially expressed genes/proteins in resected liver metastases that recurred within 6 months following liver surgery vs those that did not recur for >24 months. Expression of the identified genes/proteins in stage II (n=243) and III (n=176) tumours was analysed by immunohistochemistry on tissue microarrays. Correlation of protein levels with stage-specific outcome was assessed by uni- and multivariable analyses.Results:Both gene expression profiling and proteomics identified Maspin to be differentially expressed in colorectal liver metastases with early (<6 months) and prolonged (>24 months) time to recurrence. Immunohistochemical analysis of Maspin expression on tumour sections revealed that it was an independent predictor of time to recurrence (log-rank P=0.004) and CRC-specific survival (P=0.000) in stage III CRC. High Maspin expression was also correlated with mucinous differentiation. In stage II CRC patients, high Maspin expression did not correlate with survival but was correlated with a right-sided tumour location.Conclusion:High Maspin expression correlates with poor outcome in CRC after spread to the local lymph nodes. Therefore, Maspin may have a stage-specific function possibly related to tumour cell dissemination and/or metastatic outgrowth.

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“…24,25 Sub-cellular localization and tissue context might account for specific biological functions and differences in prognostic significance, as shown for breast 23 and colorectal cancer. 26 In melanoma, in vitro and in vivo experiments supported the idea that loss of maspin might have a role in disease progression, invasion, and metastatic dissemination, thereby suggesting that maspin might act as a tumor suppressor. 27,28 Clinically, maspin expression in nevi and melanomas has been analyzed by four different groups, with different results.…”

mentioning

confidence: 88%

Maspin expression and melanoma progression: a matter of sub-cellular localization

et al. 2014

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Maspin, a member of the serpin family of protease inhibitors, is involved in key processes of cancer progression. Its biological activity seems to be cancer and compartment specific, with the protein acting either as a suppressor or as a tumor promoter in different cancer types. Characterization of maspin expression and its sub-cellular localization in melanoma is missing, hence, we aim to investigate its possible association with melanoma prognostic factors and disease progression. Nuclear and cytoplasmic maspin expression were evaluated on 60 nevi, 152 primary lesions, and 106 melanoma metastases using tissue microarrays and immunohistochemistry. The association between maspin immunoreactivity and patient's clinic-pathological features was evaluated. Multivariate logistic models and survival analyses were performed for maspin expression in primary melanomas. Nuclear maspin was detected in 8% nevi, 49% primary melanomas, and 28% metastases, whereas cytoplasmic maspin in 12% nevi, 18% primary lesions, and 9% metastases. In univariate analysis, nuclear maspin expression in primary melanomas was significantly associated with melanoma prognostic factors (nodular histotype, tumor thickness, mitotic rate, and ulceration) and disease stage, whereas cytoplasmic maspin was observed at higher frequency in thin superficial spreading melanomas, without mitosis. In multivariate analysis, nuclear maspin remained significantly associated with risk of developing a tumor prone to disease progression and, accordingly, with significantly shorter disease-free and overall survival. In this study, maspin was expressed at highest frequency in primary lesions and when expressed in the nuclei, was significantly associated with poor prognostic markers, melanoma recurrence, and worse survival. The present study suggests a tumor-suppressive effect of cytoplasmic maspin and a tumor-promoting effect of nuclear maspin, which open the discussion on its potential use in cancer therapy. Modern Pathology (2014) 27, 412-419; doi:10.1038/modpathol.2013.157; published online 13 September 2013Keywords: biomarker; maspin; melanoma; tissue microarrays Melanoma is a malignant neoplasm that originates from melanocytes and it is characterized by frequent local recurrence, early metastasis, and refractoriness to chemotherapy and biological treatment. 1 With early diagnosis and adequate surgical treatment of primary tumors (Stage I patients), the 5-year survival rate is 495%. 2 However, once melanoma has metastasized to distant sites, life expectancy dramatically declines, with 1-year survival rate of 33% for patients with Stage IV metastatic disease. 2 Primary tumor thickness, ulceration, and mitotic rate, together with the presence of lymph node and systemic metastases, are the histopathologic criteria used for melanoma staging to predict disease outcome in terms of life expectancy and survival rates. 2 However, a significant minority of melanomas contravenes these conventional parameters and displays unpredictable clinical behavior. Furthermore, lack of...

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Shift from cytoplasmic to nuclear maspin expression correlates with shorter overall survival in node-negative colorectal cancer

Cited by 22 publications

References 36 publications

Diagnostic value of maspin in distinguishing adenocarcinoma from benign biliary epithelium on endoscopic bile duct biopsy

Diagnostic value of maspin in distinguishing adenocarcinoma from benign biliary epithelium on endoscopic bile duct biopsy

Maspin is a marker for early recurrence in primary stage III and IV colorectal cancer

Maspin expression and melanoma progression: a matter of sub-cellular localization

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