4250

SCGB2A2

secretoglobin, family 2A, member 2;SCGB2A2;secretoglobin, family 2A, member 2

mammaglobin 1|mammaglobin-A

11q13

protein-coding

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=0.016), but the Cox proportional hazard model failed to confirm that MGB1 was an independent prognostic factor (hazard ratio 1.77, P=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.

Morphologic differentiation of breast carcinoma from nonmammary malignancies in fluid specimens can be a diagnostic challenge. Immunocytochemistry is often employed in the differential diagnosis. In this study, we evaluated the expression of mammoglobin (MGB1) in body-cavity fluid specimens and compared its efficacy as a marker for metastatic breast carcinomas with that of gross cystic disease fluid protein-15 (GCDFP-15). Cell blocks from 40 fluid specimens were immunostained with monoclonal antibodies against MGB1 and GCDFP-15. They included 15 breast carcinomas and 25 nonmammary carcinomas (10 lungs, 10 ovaries, 3 gastrointestinal tracts, 1 kidney, and 1 urinary bladder). Positivity was defined as the presence of cytoplasmic staining in 10% or more carcinoma cells. Thirteen (87%) and seven (47%) breast carcinomas showed positive staining with MGB1 and GCDFP-15, respectively. Three (12%) nonmammary carcinomas (2 ovarian and 1 colonic) showed positive MGB1 staining; one (3%) nonmammary carcinoma demonstrated positive GCDFP-15 staining. The differences of MGB1 and GCDFP-15 staining between breast and nonmammary carcinomas were statistically significant (P < 0.05). Both MGB1 and GCDFP-15 are specific markers for metastatic breast carcinomas in cell block fluid specimens (88 vs. 96%). However, MGB1 is more sensitive than GCDFP-15 as a marker for metastatic breast carcinoma (87 vs. 46%).

Breast cancer (BC) is the most frequent malignant tumor in women worldwide; its recurrence is a result of undetected metastasis present at the time of primary patient treatment. The detection of cell-free RNA in plasma and serum of human subjects has found increasing applications in the field of medical diagnostics.This study aimed at evaluating plasma mammaglobin mRNA as a useful tumor marker for the diagnosis and the detection of metastasis in breast cancer at the time of diagnosis either alone or in combination with conventional serum tumor markers CA15.3 and/or CEA. This study included 40 Egyptian females with primary breast cancer and 25 with different benign breast diseases. The BC group was classified into 24 patients with localized BC and 16 patients with metastases. All patients were subjected to routine laboratory investigations, estimation of serum CA15.3 and CEA by electrochemiluminescence immunoassay and detection of plasma mammaglobin mRNA by using nested reverse transcriptase polymerase chain reaction (RT-PCR). There was a significance increase in plasma mammaglobin mRNA expression, CA15.3 and CEA levels in BC group as compared to benign group (p < 0.001). No significant difference was observed between levels of plasma mammaglobin mRNA expression in patients with tumor's size or grade. No correlation was observed with plasma mammaglobulin mRNA levels and tumor size or grading, CEA and CA15.3. There was a significant difference (p < 0.05) and a positive correlation between CA 15.3 and CEA levels in patients with tumor size and grading. expression of plasma mammaglobin mRNA has the highest sensitivity, specificity and diagnostic accuracy for both BC and BC with metastasis (75%, 92% & 81.5%) and (87.5%, 45.8% & 62.5%), respectively. To improve diagnostic efficacy of BC, the use of combined tests, expression of plasma mammaglobin mRNA and CA 15.3 improved the sensitivity, specificity and diagnostic accuracy to 90%, 80% & 86.2%, respectively; as well as in BC with metastasis to 100%, 79.2%, & 87.5%, respectively. In conclusion, plasma mammaglobin mRNA alone or in combination with CA15.3 may be used as a valuable noninvasive approach for the diagnosis and the detection of metastasis in breast cancer at the time of diagnosis.

AIM: To evaluate the value of peripheral blood mammaglobin (MG) gene expression for diagnosis and prediction of metastasis in breast cancer patients. METHODS: MG expression was detected by nested reverse-transcription polymerase chain reaction in the peripheral blood of 46 females (32 breast cancer, 12 benign breast lesions, 2 no breast abnormalities). In total 28 breast cancer patients were followed up through a period of 34 months for the development of metastasis. RESULTS: MG expression was detected in 16/32 (50%) breast cancer patients but not in patients with benign lesions or healthy participants. Five patients had metastasis at diagnosis. During the 34 months of follow up, five more MG-positive patients showed metastatic lesions and none of the MG negative patients who were followed up developed metastasis. CONCLUSION: The study suggests blood MG expression is a specific molecular marker for detection of occult mammary carcinoma cells of patients with operable breast cancer. It might be of value as a predictor of subsequent metastasis. Large-scale studies and longer follow-up periods are needed.