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Molecular characteristics of breast cancer according to clinicopathological factors.

ABSTRACT: The purpose of the present study was to evaluate the correlation between molecular factors such as BRCA1 DNA repair associated (BRCA1), checkpoint kinase 2 (CHEK2) and nucleotide binding oligomerization domain containing 2 (NOD2) gene mutations and clinicopathological factors in patients with breast cancer (BC). Prognostic factors were analyzed in BC patients with confirmed BRCA1 (n=73), CHEK2 (n=51) and NOD2 (n=31) mutations. The control group was selected from BC patients without mutations (n=392). The BRCA-associated cancer cases were significantly more often triple negative compared with sporadic cancer (62% vs. 14%; P=0.0001). Luminal B HER2-positive and HER2-positive non-luminal subtypes were observed more often in the control group (33 and 17%). The luminal A subtype was detected in 53% of CHEK2 mutation carriers and 45% of NOD2 mutation carriers. A lower histological grade was observed significantly more often in patients with CHEK2 mutations in comparison with the control group (88 vs. 69%; P=0.003). Lymph nodes without metastases were reported more frequently in NOD2 mutation carriers (74 vs. 54%; P=0.038), in BRCA1 mutations (73 vs. 54%; P=0.004) and, although not significantly, in CHEK2 mutation carriers (69 vs. 54%; P=0.071) compared with the control group. In conclusion, BRCA1 mutation was associated with TNBC and the luminal B HER2 (-) subtype. HER2-positive subtypes were characteristic of the control group. CHEK2 and NOD2 mutation carriers had a more favorable profile of prognostic factors.

SUBMITTER: Huszno J

PROVIDER: S-EPMC6587005 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Molecular characteristics of breast cancer according to clinicopathological factors.

Huszno Joanna J Kolosza Zofia Z

Molecular and clinical oncology 20190528 2

The purpose of the present study was to evaluate the correlation between molecular factors such as BRCA1 DNA repair associated (BRCA1), checkpoint kinase 2 (CHEK2) and nucleotide binding oligomerization domain containing 2 (NOD2) gene mutations and clinicopathological factors in patients with breast cancer (BC). Prognostic factors were analyzed in BC patients with confirmed BRCA1 (n=73), CHEK2 (n=51) and NOD2 (n=31) mutations. The co ...[more]

PMID: 31281656

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Project description:Despite advances in treatment, up to 30% of patients with early breast cancer (BC) experience distant disease relapse. However, a comprehensive understanding of tumor spread and site-specific recurrence patterns remains lacking. This retrospective case-control study included 103 consecutive patients with metastatic BC admitted to our institution (2000-2013). Cases were matched according to age, tumor biology, and clinicopathological features to 221 patients with non-metastatic BC (control group). The median follow-up period among the 324 eligible patients was 7.3 years. While relatively low values for sensitivity (71%) and specificity (56%) were found for axillary lymph node (ALN) involvement as an indicator of risk and pattern of distant relapse, nodal status remained the most powerful predictor of metastases (OR: 3.294; CL: 1.9-5.5). Rates of dissemination and metastatic efficiency differed according to molecular subtype. HER2-positive subtypes showed a stronger association with systemic spread (OR: 2.127; CL: 1.2-3.8) than other subgroups. Classification as Luminal or Non-Luminal showed an increased risk of lung and distant nodal recurrence, and a decreased risk in bone metastases in the Non-Luminal group (OR: 2.9, 3.345, and 0.2, respectively). Tumors with HER2 overexpression had a significantly high risk for distant relapse (OR: 2.127) compared with HER2-negative tumors and also showed higher central nervous system (CNS) and lung metastatic potential (OR: 5.6 and 2.65, respectively) and low risk of bone disease progression (OR: 0.294). Furthermore, we found significant associations between biological profiles and sites of recurrence. A new process of clinical/diagnostic staging, including molecular subtypes, could better predict the likelihood of distant relapses and their anatomical location. Recognition and appreciation of clinically distinct molecular subtypes may assist in evaluation of the probability of distant relapses and their sites. Our analysis provides new insights into management of metastatic disease behavior, to lead to an optimal disease-tailored approach and appropriate follow-up.

Project description:BackgroundThe function of tropomyosin 2 (TPM2) in breast cancer is still far understudied. In this study, we aim to explore the roles of TPM2 in breast cancer progression.MethodsThis research included 155 breast cancer tissues. The expression of TPM2 was analyzed by immunohistochemical staining and grading. The mRNA expression of TPM2 in pan-cancer was analyzed with The Cancer Genome Atlas (TCGA) data plate form. The differential expression of TPM2 protein and the differential promoter methylation level of TPM2 between breast cancer tissues and normal breast tissues were analyzed by the UALCAN online database. The relationship between TPM2 and signaling pathways was interpreted by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) pathway enrichment analyses. The survival curve of TPM2 was analyzed across the Kaplan-Meier plotter online database. Furthermore, the relationship between TPM2 expression and infiltrating macrophages was validated through in vitro co-culture experiments.ResultsTPM2 expression was significantly down-regulated in breast cancer samples. In addition, TPM2 expression was correlated with lymph node metastasis and high-grade histopathological morphology. The receiver operating characteristic (ROC) curve indicated that TPM2 expression could well distinguish between normal breast tissue and breast cancer tissue. TPM2 may have potential value in breast cancer diagnosis. Bioinformatics analysis illustrated that TPM2 was mainly involved in extracellular matrix organization, collagen fibril organization, cell junction assembly, focal adhesion, cAMP signaling pathway, estrogen signaling pathway, Wnt signaling pathway, and adaptive immune system. TPM2 expression was correlated with immune infiltrating cells and immune checkpoint molecules. Our in vitro co-culture experiments showed that the M2 macrophages could upregulate the expression of TPM2.ConclusionTPM2 may play key roles in breast cancer occurrence and development, especially in cancer metastasis. TPM2 may be a potential biomarker for breast cancer diagnosis.

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Molecular characteristics of breast cancer according to clinicopathological factors.

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Molecular characteristics of breast cancer according to clinicopathological factors.

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