{"id":63257,"date":"2024-12-30T11:08:49","date_gmt":"2024-12-30T11:08:49","guid":{"rendered":"https:\/\/biomedpharmajournal.org\/?p=63257"},"modified":"2025-01-06T18:40:55","modified_gmt":"2025-01-06T18:40:55","slug":"strong-mammaglobin-a-expression-in-tumor-tissue-as-a-risk-factor-for-metastasis-in-balinese-breast-cancer-patients","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol17no4\/strong-mammaglobin-a-expression-in-tumor-tissue-as-a-risk-factor-for-metastasis-in-balinese-breast-cancer-patients\/","title":{"rendered":"Strong Mammaglobin-A Expression in Tumor Tissue as a Risk Factor for Metastasis in Balinese Breast Cancer Patients"},"content":{"rendered":"

Introduction <\/strong><\/p>\n

Based on Globocan 2022 data, breast cancer occupied 11.6% of it, or around 2,296,840 people affected. The incidence of breast cancer in America is around 92\/100,000 women with an 18% mortality rate.1<\/sup> Based on the Pathology Based Registration in Indonesia, breast cancer ranks first with a prevalence of 18.6%. It is estimated that the incidence rate of breast cancer in Indonesia is 12\/100,000 women.2<\/sup><\/p>\n

Metastasis in breast cancer is the migration of breast malignant cells to other tissues of the body. Metastasis indicates the formation of a secondary implant located far from the primary tumor. Breast cancer metastasis can spread through lymphatic system to the lymph nodes, and hematogenously to other organs. The most often affected organs by distant metastases from breast cancer include the brain (less than 5%), pleura (5-15%), lung (5-15%), bone (40-75%), and liver (3-10%). Both hematogenous and lymphogenous metastasis pose a serious threat to breast cancer patients.3<\/sup><\/p>\n

Metastasis detection is essential in breast cancer patients because it significantly affect the long-term survival of the patients. The earliest detection of metastasis in breast cancer patients is better, since many of the patients, especially in Indonesia is diagnosed in late stage. There are many biomarker available for breast cancer such as carcinoembryonic antigen (CEA), cancer antigen (CA) 15-3, CA 27-29. But these biomarkers still has several limitation, one of them is lack of sensitivity. 4<\/sup> Mammaglobin (hMAG) A, also known as Mammaglobin (MGB) 1 or Uteroglobin (UGB) 2 or Secretoglobin (SCGB) 2A2, is only overexpressed in breast cancer.5<\/sup> Mammaglobin A, which belongs to the secretory protein family, is overexpressed in 40\u201380% of instances of breast cancer, both primary and metastatic. Previous study found that Balinese race with metastatic breast cancer has higher mRNA expression. This showed Mammaglobin A is employed as a diagnostic biomarker in individuals with breast cancer because of its distinct and universal expression features.4<\/sup> Mammaglobin A expression profile is specific to the breast organ, so Mammaglobin A is considered a prominent biomarker for breast cancer cell detection. Currently, Mammaglobin A can be used as a clinical biomarker to detect metastatic breast cancer larger than 0.2 mm2<\/sup>.6\u20138<\/sup> Previous study evaluated Mammaglobin A is only focus in breast cancer in general, and lack information regarding the effect of Mammaglobin A expression in tumor tissue with the risk of metastasis. Therefore, the purpose of this study was to assess the association between mammaglobin A expression and metastasis in Balinese patients with breast cancer.<\/p>\n

Materials and Methods <\/strong><\/p>\n

This study is a case-control study, started from January to December 2023 in the medical record room, anatomic pathology, and data from the Oncology department of Prof. I.G.N.G. Ngoerah Hospital Bali. All Balinese patients with breast cancer who underwent treatment at Prof. I.G.N.G. Ngoerah Hospital Bali with complete medical records were included in this study. Meanwhile, the exclusion criteria in this study included breast cancer patients who had performed immunohistochemical examinations outside Prof. I.G.N.G. Ngoerah Hospital Bali and male breast cancer patients.<\/p>\n

This study evaluated the clinicopathological data which includes age, menstrual status, tumor size, parity, distant metastasis, lymph node metastasis, histopathological grading, subtypes, collected from the medical record, and Mammaglobin A expression which was carried out by immunohistochemistry (IHC) of the formalin-fixed paraffin-embedded specimen using monoclonal antibody anti-Mammaglobin A. Two pathologists then assessed the IHC data using a 0\u20133 scoring system depending on the expression following staining (Table 1). A score of 0-1 is categorized as a weak expression, while a score 2 is categorized as a strong expression.<\/p>\n

Table 1: Mammaglobin A category based on IHC results<\/strong><\/p>\n\n\n\n\n\n\n\n
IHC results<\/strong><\/td>\nScoring<\/strong><\/td>\n<\/tr>\n
Strong staining<\/td>\n3<\/td>\n<\/tr>\n
Moderate staining<\/td>\n2<\/td>\n<\/tr>\n
Weak staining<\/td>\n1<\/td>\n<\/tr>\n
No staining<\/td>\n0<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

The data were analyzed using the SPSS software. The stages of data analysis were as follows: univariate analysis, bivariate analysis using Chi-square test to obtained Relative risk (RR) and independent t-test or Mann-Whitney for numerical data. The results are considered significant if p-value <0.05.<\/p>\n

Results<\/strong><\/p>\n

A total of 48 research subjects were recruited for this study and split into two groups: 24 subjects were assigned to the metastasis group and another 24 patients to the non-metastasis group. Table 2 displays the data characteristics results.<\/p>\n

Table 2: Data Characteristics<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
Variables<\/strong><\/td>\nGroup<\/strong><\/td>\nP-value<\/strong><\/td>\n<\/tr>\n
Metastasis (n=24)<\/strong><\/td>\nNo metastasis (n=24)<\/strong><\/td>\n<\/tr>\n
Age, mean\u00b1SD<\/td>\n46.00\u00b113.03<\/td>\n48.00\u00b17.07<\/td>\n0.905a<\/sup><\/td>\n<\/tr>\n
Menstrual Status, n (%)<\/td>\n<\/td>\n<\/td>\n<\/td>\n<\/tr>\n
Premenopause<\/td>\n9 (37.5%)<\/td>\n6 (25.0%)<\/td>\n0.350b<\/sup><\/td>\n<\/tr>\n
Postmenopause<\/td>\n15 (62.5%)<\/td>\n18 (75.0%)<\/td>\n<\/td>\n<\/tr>\n
Parity, mean\u00b1SD<\/td>\n2.00\u00b11.50<\/td>\n2.5\u00b10.70<\/td>\n0.486 a<\/sup><\/td>\n<\/tr>\n
Tumor size, n (%)<\/td>\n<\/td>\n<\/td>\n<\/td>\n<\/tr>\n
T1<\/td>\n0 (0.0%)<\/td>\n1 (4.2%)<\/td>\n<0.001b<\/sup><\/td>\n<\/tr>\n
T2<\/td>\n0 (0.0%)<\/td>\n22 (91.7%)<\/td>\n<\/td>\n<\/tr>\n
T3<\/td>\n4 (16.7%)<\/td>\n1 (4.2%)<\/td>\n<\/td>\n<\/tr>\n
T4<\/td>\n1 (4.2%)<\/td>\n0 (0.0%)<\/td>\n<\/td>\n<\/tr>\n
T4a<\/td>\n1 (4.2%)<\/td>\n0 (0.0%)<\/td>\n<\/td>\n<\/tr>\n
T4b<\/td>\n13 (54.2%)<\/td>\n0 (0.0%)<\/td>\n<\/td>\n<\/tr>\n
T4c<\/td>\n4 (16.7%)<\/td>\n0 (0.0%)<\/td>\n<\/td>\n<\/tr>\n
T4d<\/td>\n1 (4.2%)<\/td>\n0 (0.0%)<\/td>\n<\/td>\n<\/tr>\n
Lymph node metastasis, n (%)<\/td>\n<\/td>\n<\/td>\n<\/td>\n<\/tr>\n
0<\/td>\n0 (0.0%)<\/td>\n11 (45.8%)<\/td>\n<0.001*b<\/sup><\/td>\n<\/tr>\n
1<\/td>\n14 (58.3%)<\/td>\n12 (50.0%)<\/td>\n<\/td>\n<\/tr>\n
2<\/td>\n6 (25.0%)<\/td>\n1 (4.2%)<\/td>\n<\/td>\n<\/tr>\n
3<\/td>\n4 (16.7%)<\/td>\n0 (0.0%)<\/td>\n<\/td>\n<\/tr>\n
Histopathology grading, n (%)<\/td>\n<\/td>\n<\/td>\n<\/td>\n<\/tr>\n
1<\/td>\n3 (12.5%)<\/td>\n2 (8.3%)<\/td>\n<0.406b<\/sup><\/td>\n<\/tr>\n
2<\/td>\n8 (33.3%)<\/td>\n13(54.2%)<\/td>\n<\/td>\n<\/tr>\n
3<\/td>\n13 (54.2%)<\/td>\n9 (37.5%)<\/td>\n<\/td>\n<\/tr>\n
Number of organ metastases, n (%)<\/td>\n<\/td>\n<\/td>\n<\/td>\n<\/tr>\n
1<\/td>\n12 (50.0%)<\/td>\n<\/td>\n<\/td>\n<\/tr>\n
2<\/td>\n10 (41.7%)<\/td>\n<\/td>\n<\/td>\n<\/tr>\n
3<\/td>\n2 (8.3%)<\/td>\n<\/td>\n<\/td>\n<\/tr>\n
Subtypes, n (%)<\/td>\n<\/td>\n<\/td>\n<\/td>\n<\/tr>\n
Luminal A<\/td>\n3 (12.5%)<\/td>\n6 (25.0%)<\/td>\n0.071b<\/sup><\/td>\n<\/tr>\n
Luminal B<\/td>\n3 (12.5%)<\/td>\n4 (16.7%)<\/td>\n<\/td>\n<\/tr>\n
Luminal-HER 2<\/td>\n3 (12.5%)<\/td>\n5 (20.8%)<\/td>\n<\/td>\n<\/tr>\n
HER 2<\/td>\n6 (25.0%)<\/td>\n5 (20.8%)<\/td>\n<\/td>\n<\/tr>\n
TNBC<\/td>\n9 (37.5%)<\/td>\n4 (16.7%)<\/td>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Notes: a<\/sup>independent t-test,b<\/sup> Chi-Square,*Significant<\/p>\n

The highest number of organ metastases obtained was 1 location, the details of which are presented in Table 3 with the most results being the lung area with the results of 5 (20.8%) subjects.<\/p>\n

Table 3: Location of distant metastasis<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
Location of distant metastasis<\/strong><\/td>\nn (%)<\/strong><\/td>\n<\/tr>\n
Lung<\/td>\n5 (20.8%)<\/td>\n<\/tr>\n
Lung, liver<\/td>\n4 (16.7%)<\/td>\n<\/tr>\n
Hepar<\/td>\n3 (12.5%)<\/td>\n<\/tr>\n
Lungs, bones<\/td>\n3 (12.5%)<\/td>\n<\/tr>\n
Bones<\/td>\n2 (8.3%)<\/td>\n<\/tr>\n
Brain<\/td>\n1 (4.2%)<\/td>\n<\/tr>\n
Bone, spine<\/td>\n1 (4.2%)<\/td>\n<\/tr>\n
Lung, contralateral of breast<\/td>\n1 (4.2%)<\/td>\n<\/tr>\n
Lung, liver, brain<\/td>\n1 (4.2%)<\/td>\n<\/tr>\n
Lung, bone, contralateral of breast<\/td>\n1 (4.2%)<\/td>\n<\/tr>\n
Hepar, bone<\/td>\n1 (4.2%)<\/td>\n<\/tr>\n
Lung, liver, brain<\/td>\n1 (4.2%)<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

The results of IHC on Mammaglobin A can be seen in Figure 1. This study found 18 (37.5%) patients categorized as having strong expression of Mammaglobin A, while 30 (62.5%) others had weak expression of Mammaglobin A.<\/p>\n\n\n\n
\"\"<\/td>\nFigure 1: Mammaglobin A expression of breast cancer. A) no-stain, B) weak-staining, C) moderate-staining, D) strong-staining.<\/strong>Click here to View Figure<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Table 3 presents an analysis of the association between metastasis and mammaglobin A expression. It showed that 66.7% of samples with breast cancer metastases had strong Mammaglobin A expression. Meanwhile, the no metastasis showed that 91.7% of the patients had a weak expression of Mammaglobin A. It also showed that patients with strong expression of Mammaglobin A have a 22.00 times higher risk of developing metastasis compared to patients with negative or low expression of Mammaglobin A. This showed that patients with breast cancer who have spread compared to those who have not had any metastases have significantly different expression levels of mammaglobin A (p<0.001; 95%CI: 4.10 – 117.80) (Table 4).<\/p>\n

Table 4: Association between metastasis and mammaglobin A expression<\/strong><\/p>\n\n\n\n\n\n\n\n
Variables<\/strong><\/td>\nGroup<\/strong><\/td>\nOR<\/strong><\/td>\nP-value<\/strong><\/td>\n95%CI<\/strong><\/td>\n<\/tr>\n
Metastasis<\/strong><\/td>\nNo metastasis<\/strong><\/td>\n<\/tr>\n
Mammaglobin A<\/td>\n<\/td>\n<\/td>\n<\/td>\n<\/td>\n<\/td>\n<\/tr>\n
Strong expression (\u22652)<\/td>\n16 (66.7%)<\/td>\n2 (8.3%)<\/td>\n22.00<\/td>\n<0.001a<\/sup><\/td>\n4.10 – 117.80<\/td>\n<\/tr>\n
Weak expression (0-1)<\/td>\n8 (33.3%)<\/td>\n22 (91.7%)<\/td>\n<\/td>\n<\/td>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Description: a <\/sup>Chi-Square<\/p>\n

Based on the 2×2 bivariate chi-square analysis, these results indicate that the sensitivity rate of Mammaglobin A as a metastasis marker is quite good (66.7%), and has a high positive predictive value (PPV) (88.9%). This indicates that when the patient’s Mammaglobin A result is positive, it has a positive prediction rate of 88.9% for the occurrence of metastasis (Table 5).<\/p>\n

Table 5: Diagnostic value of Mammaglobin A in metastatic breast cancer<\/strong><\/p>\n\n\n\n\n
Marker<\/strong><\/td>\nSensitivity<\/strong><\/td>\nSpecificity<\/strong><\/td>\nPositive Predictive Value (PPV)<\/strong><\/td>\nNegative Predictive Value (NPV)<\/strong><\/td>\n<\/tr>\n
Mammaglobin A<\/td>\n66.7<\/td>\n91.7<\/td>\n88.9<\/td>\n73.3<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Discussion<\/strong><\/p>\n

Age, menstrual state, parity, histopathological grade, and breast cancer subtype did not significantly differ from the incidence of metastasis. But eventually, there were significant differences in tumor size and the presence of lymph node metastasis between the two groups. The most common location for distant metastasis in this study is the lung. This is consistent with a prior study that discovered lung metastases were identified in 60\u201370% of breast cancer patients who ultimately passed away.9<\/sup> Breast cancer has a tendency to metastasize certain organs, most often the bones and lungs, liver, and brain.10<\/sup> Most mortality from breast cancer are caused by metastasis, or the tumor cells spreading throughout the body. The survival rate for individuals with lung metastasis is still extremely low, despite advancements in the numerous medicines available for the condition, including as targeted therapy, chemotherapy, and radiotherapy.11<\/sup><\/p>\n

Breast cancer is a form of malignant tumor that is commonly seen in clinical settings. It varies widely in terms of molecular subtypes, therapeutic options, and the degree of disease variety. The majority of patients’ safety, quality of life, and physical and mental health are all impacted by this diversity, which also has an impact on the prognosis of the condition. Consequently, early detection of breast cancer depends on pathological diagnosis at the molecular level, which calls for special attention in the development of more precise detection techniques and the identification of useful indicators for diagnostic and prognostic reasons.12<\/sup><\/p>\n

One well-known particular marker for breast cancer is mammaglobin expression, which is positively correlated with tumor stage, histological grade, lymph node metastasis, and endocrine status. In this investigation, we discovered a strong correlation between breast cancer patients’ metastases and strong expression of mammaglobin A. This discovery is consistent with earlier research that found mammaglobin overexpression to be a possible marker of metastasis in breast cancer patients and linked to metastasis to lymph nodes.12<\/sup><\/p>\n

These results are consistent with a prior study which discovered that a poor prognosis was related to positive expression of mammaglobin A (P<0.001; 95%CI 1.48-2.91).13<\/sup> Another case-control study also found that overexpression of Mammaglobin A mRNA was a risk factor for breast cancer by 9 times (p = 0.002; 95% CI = 2.15 – 37.66) compared to low Mammaglobin A mRNA expression. In addition, Mammaglobin A mRNA overexpression increased the risk of breast cancer metastases by 7.36-fold (p = 0.013; 95% CI = 1.34 – 40.55).6<\/sup><\/p>\n

Mammaglobin A shows an excellent ability to detect breast cancer. This can be seen in the Positive Predictive Value (PPV) value of Mammaglobin A against breast cancer metastasis of 88.9%. This shows that, a total of 88.9% of patients with mammaglobin A expression will experience metastasis, in this study mostly in the lung, liver, and or bone organs. This is in line with the previous study which found mammaglobin A has a specificity of 100% and sensitivity of 81.5%.12 <\/sup>Furthermore, Mammaglobin A continues to have the highest specificity (100%) and a strong PPV value (74%) when compared to CEA and CA15-3.14<\/sup> However, this study still has several limitations such as this is only a case-control study with a lack of time to evaluate the disease progression.<\/p>\n

Conclusion <\/strong><\/p>\n

Balinese breast cancer patients with strong Mammaglobin A expression in tumor tissue has higher risk of metastasis.<\/p>\n

Acknowledgment\u00a0<\/strong><\/p>\n

The authors would like to thank Pathologist at Prof. Dr. I.G.N.G Ngoerah Denpasar Hospital Bali for providing the expertise and experience in tumor tissue examination<\/p>\n

Funding Sources<\/strong><\/p>\n

The author(s) received no financial support for the research, authorship, and\/or publication of this article.\u00a0<\/strong><\/p>\n

Conflict of Interest<\/strong><\/p>\n

The author(s) do not have any conflict of interest.<\/p>\n

Data Availability Statement<\/strong><\/p>\n

This statement does not apply to this article.<\/p>\n

Ethics Statement<\/strong><\/p>\n

This research has received a research permit from the research ethics committee of Udayana University \/ Prof. I.G.N.G. Ngoerah Hospital Bali with number 388 \/ UN14.2.2.VII.14 \/ LT \/ 2023.<\/p>\n

Informed Consent Statement<\/strong><\/p>\n

This study did not involve human participants, and therefore, informed consent was not required.\u00a0<\/strong><\/p>\n

Clinical Trial Registration<\/strong><\/p>\n

This research does not involve any clinical trials.\u00a0<\/strong><\/p>\n

Author\u2019s Contribution<\/strong><\/p>\n

Putu Anda Tusta Adiputra: Conceptualization, Analysis, Writing \u2013 Review & Editing<\/p>\n

I Wayan Sudarsa: Methodology, Analysis, Writing \u2013 Review & Editing<\/p>\n

Gede Budhi Setiawan: Data Collection, Analysis, Writing \u2013 Review & Editing<\/p>\n

Ida Bagus Made Suryawisesa: Conceptualization, Analysis, Writing \u2013 Review & Editing<\/p>\n

Kadek Yudi Fajar Mahendra: Data Collection, Writing \u2013 Original Draft<\/p>\n

References<\/strong><\/p>\n

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    Introduction Based on Globocan 2022 data, breast cancer occupied 11.6% […]<\/p>\n","protected":false},"author":15,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[119],"tags":[],"class_list":["post-63257","post","type-post","status-publish","format-standard","hentry","category-vol17no4"],"_links":{"self":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/63257","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/users\/15"}],"replies":[{"embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/comments?post=63257"}],"version-history":[{"count":5,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/63257\/revisions"}],"predecessor-version":[{"id":63536,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/63257\/revisions\/63536"}],"wp:attachment":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/media?parent=63257"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/categories?post=63257"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/tags?post=63257"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}