Mammaglobin Is Associated With Low-Grade, Steroid Receptor-Positive Breast Tumors From Postmenopausal Patients, and Has Independent Prognostic Value for Relapse-Free Survival Time

Span, Paul N.; Waanders, Esmé; Manders, Peggy; Heuvel, J. J. T. M.; Foekens, John A.; Watson, Mark A.; Beex, L.V.A.M.; Sweep, Fred C.G.J.

doi:10.1200/jco.2004.01.072

Cited by 76 publications

(65 citation statements)

References 18 publications

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“…Indeed, MGB1 has steroid-responsive elements in its promoter region, 1 and recent analysis based on mRNA expression also revealed an association of MGB1 with ER expression. 26,27 In conclusion, MGB1 is a highly specific marker of breast cancers, and its expression was detected in about half the breast cancers examined. The expression of MGB1 was correlated with that of ER, but was unaffected by other clinicopathological features, including pathological stage, HER2 gene status and disease-free survival rate.…”

Section: Discussionmentioning

confidence: 87%

Breast-specific expression of MGB1/mammaglobin: an examination of 480 tumors from various organs and clinicopathological analysis of MGB1-positive breast cancers

Sasaki

Tsunoda

Hatanaka³

et al. 2007

Modern Pathology

122

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Previously, we used the reverse transcription-polymerase chain reaction (RT-PCR) to show that mammaglobin (MGB1) can serve as a differential marker of breast cancer metastasis from primary lung cancer. However, mRNA-based methods are not appropriate for use in clinical practices. In this study, we examined MGB1 protein expression in 480 tumors from various organs using immunohistochemical detection and a tissue microarray technique. Breast cancers expressing MGB1 were also analyzed clinicopathologically to determine whether these cancers constitute a characteristic subset. Immunohistochemically, MGB1 was expressed specifically in breast cancers. Of the other cancers examined, including 29 of the head and neck, eight of the thyroid, 106 of the lung, 35 of the gastrointestinal tract, three of the pancreas, 14 of the uterine cervix and 13 of the ovary, none were positive for MGB1 except a proportion of salivary gland tumors (6/11, 55%) and endometrial cancers (3/23, 13%). Among the 238 breast cancers, MGB1 was expressed in 114 (48%), most of which were classified histologically as invasive duct or lobular carcinomas. Clinicopathologically, MGB1 expression was associated with positive expression of estrogen receptors and negative expression of CK5, but not with pathological stage, HER2 gene amplification or p53 immunoreactivity. Kaplan-Meier analysis revealed prolonged disease-free survival in patients with MGB1-positive breast cancers (log rank test, P ¼ 0.016), but the Cox proportional hazard model failed to confirm that MGB1 was an independent prognostic factor (hazard ratio 1.77, P ¼ 0.1755). In terms of practical diagnosis, MGB1 immunohistochemistry can serve as a differential marker of breast cancer metastasis from primary lung cancer for two reasons. Firstly, HER2-positive breast cancer frequently lacks estrogen receptor expression, but MGB1 is expressed in about half of this subtype. Secondly, as primary lung adenocarcinomas may express estrogen receptors, MGB1 expression provides further discrimination of the origin of breast cancers.

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Section: Discussionmentioning

confidence: 87%

Breast-specific expression of MGB1/mammaglobin: an examination of 480 tumors from various organs and clinicopathological analysis of MGB1-positive breast cancers

Sasaki

Tsunoda

Hatanaka³

et al. 2007

Modern Pathology

122

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“…Previous studies have shown that mammaglobin mRNA levels were detectable at higher levels in breast tumors compared with normal breast tissue, and mammaglobin was not expressed at the RNA level in several normal tissues (3). Moreover, mammaglobin protein expression in breast tumors was observed at high frequency (3,15,16) independent of stage, grade, or histology (2). This evidence of breast tissue specificity has led to the application of mammaglobin as a marker for metastatic spread of breast cancer to lymph nodes (5).…”

Section: Discussionmentioning

confidence: 99%

Identification of Mammaglobin as a Novel Serum Marker for Breast Cancer

Bernstein

Godbold

Raptis

et al. 2005

Clinical Cancer Research

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Purpose: Early detection of breast cancer has implications for the management and treatment of patients with this disease. Currently, there exist no highly sensitive and specific serologic biomarkers for detection of breast cancer. Mammaglobin is predicted to be a secreted protein, and expression of this gene seems to be highly specific in breast cancer. The present studies were undertaken to develop the mammaglobin protein as a serum biomarker for detection of breast cancer. Experimental Design: We characterized the mammaglobin protein as a secreted, 14-to 21-kDa species, which is likely post-translationally processed based on its predicted 7-kDa size. Immunostaining for mammaglobin was conducted. An ELISA was developed for the detection of the mammaglobin protein in serum, and levels were compared between women with and without breast cancer. A receiver operating characteristic curve was used to show sensitivity and specificity for cut points on the continuous mammaglobin scale. Results:The protein was detectable by immunostaining in 72% of breast tumors and not in other tumor types.The ELISA was highly sensitive and specific for detection of mammaglobin protein in tissue culture fluids of breast cancer cells and sera of breast cancer patients. The ELISA differentiated healthy women from those with breast cancer with accurate, repeatable results across time and under varying storage conditions. Conclusion: Our results indicate that mammaglobin, as measured by the ELISA, holds significant promise for breast cancer screening with the realistic potential to impact management of this disease.

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“…19 A series of 183 patients with unilateral, resectable breast cancers who had undergone resection of their primary tumors between November 1987 and December 1997 were selected based on the availability of RNA in the Original Article tumor bank of the Department of Laboratory Medicine of the RUNMC. 20 This bank contains material from breast cancer patients of 7 different hospitals of the Comprehensive Cancer Centre East in the Netherlands. The inclusion and exclusion criteria have been described earlier.…”

Section: Patientsmentioning

confidence: 99%

“…The inclusion and exclusion criteria have been described earlier. 20 Postoperative radiotherapy was given to the breast after an incomplete resection or after breast-conserving treatment, or parasternal when the tumor was medially localized. Axillary irradiation was given in the case of positive lymph nodes.…”

Section: Patientsmentioning

confidence: 99%

Hypoxic regulation and prognostic value of LAMP3 expression in breast cancer

Nagelkerke

Mujčić

Bussink

et al. 2011

Cancer

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BACKGROUND: LAMP3 is a newly described hypoxia regulated gene of potential interest in hypoxia-induced therapy resistance and metastasis. The prognostic value of LAMP3 in breast cancer was investigated. METHODS: Expression levels of LAMP3 in breast cancer cell lines and patient tissues were determined by real-time polymerase chain reaction and in a tissue microarray by immunohistochemistry. Immunofluorescent staining was used to evaluate the distribution of LAMP3 in tumor xenografts relative to pimonidazole. Kaplan-Meier analysis as well as multivariate Cox regression survival analyses were performed. RESULTS: LAMP3 was variably expressed in breast cancer cell lines and induced in an oxygen concentration-dependent manner. LAMP3 protein expression colocalized with hypoxic areas in breast cancer xenografts. LAMP3 mRNA was higher in breast tumors from patients with node-positive (P ¼ .019) and/or steroid hormone receptor-negative tumors (P < .001). Breast cancer patients with high LAMP3 mRNA levels had more locoregional recurrences (P ¼ .032 log-rank). This was limited to patients treated with lumpectomy and radiotherapy as primary treatment (n ¼ 53, P ¼ .009). No association with metastasis-free survival was found. In multivariate Cox regression analysis, LAMP3 remained as a statistically independent prognostic factor for locoregional recurrence (hazard ratio, 2.76; 95% confidence interval, 1.01-7.5; P ¼ .048) after correction for menopausal status, histologic grade, tumor size, nodal status, therapy, and steroid hormone receptor status. LAMP3 protein in breast cancer tissue proved also to be of prognostic relevance. CONCLUSIONS: Evidence was provided for an association of LAMP3 with tumor cell hypoxia in breast cancer xenografts. In the current breast cancer cohorts, LAMP3 had independent prognostic value.

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Mammaglobin Is Associated With Low-Grade, Steroid Receptor-Positive Breast Tumors From Postmenopausal Patients, and Has Independent Prognostic Value for Relapse-Free Survival Time

Abstract: These results demonstrate that the assessment of the tumor mRNA expression level of the breast-specific protein mammaglobin could be useful to stratify patients for individual adjuvant treatment strategies.

Cited by 76 publications

References 18 publications

Breast-specific expression of MGB1/mammaglobin: an examination of 480 tumors from various organs and clinicopathological analysis of MGB1-positive breast cancers

Breast-specific expression of MGB1/mammaglobin: an examination of 480 tumors from various organs and clinicopathological analysis of MGB1-positive breast cancers

Identification of Mammaglobin as a Novel Serum Marker for Breast Cancer

Hypoxic regulation and prognostic value of LAMP3 expression in breast cancer

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