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Relevance of systems biological approach in the differential diagnosis of invasive lobular carcinoma & invasive ductal carcinoma.

ABSTRACT: Breast cancer is a malignant neoplasm originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. ILCs and IDCs vary from each other with respect to various histological, biological and clinical features. Remarkably, ductal tumors tending to form glandular structures, whereas lobular tumors are less cohesive and tends to invade in single file. The high degree of similarity in the prognoses of IDC and ILC makes it beneficial to develop a differential diagnostic protocol to classify the two conditions. The main goal of the study is to construct the genetic regulatory network from the microarray data using biological knowledge and constraint-based inferences, in order to explore the potential significant gene regulatory networks that can differentiate IDC and ILC and thereby understand the complex interactions that are influenced by the genetic networks. Out of the 54676 genes present on the GPL570 platform- 29 genes exhibited 4 fold up regulation in case of IDC and 22 in the case of ILC. The ductal and lobular tumors displayed a striking difference in the expression of genes associated with cell adhesion, protein folding, and protein phosphorylation and invasion. Construction of separate gene regulation networks for IDC and ILC on the basis of gene expression altercation can be utilized in understanding the distinction in the possible mechanism that underlies the pathological differences between the two, which can be exploited in identifying diagnostic or therapeutic targets.

SUBMITTER: Ragunath PK

PROVIDER: S-EPMC3346022 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Relevance of systems biological approach in the differential diagnosis of invasive lobular carcinoma & invasive ductal carcinoma.

Ragunath P K PK Reddy B Vanaja BV Abhinand P A PA Ahmed Shiek S S J SS

Bioinformation 20120430 8

Breast cancer is a malignant neoplasm originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. ILCs and IDCs vary from each other with respect to various histological, biological and clinical features. Remarkably, ductal tumors tending to form glandular structures, whereas lobular tumors are less cohesive and tends to invade in single file. The high degree of similarity in the prognoses of IDC and ILC makes it beneficial to ...[more]

PMID: 22570516

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Project description:Invasive lobular breast carcinoma (ILC) is the second most common breast carcinoma (BC) subtype and is mainly driven by loss of E-cadherin expression. Correct classification of BC as ILC is important for patient treatment. This study assessed the degree of agreement among pathologists for the diagnosis of ILC. Two sets of hormone receptor (HR)-positive/HER2-negative BCs were independently reviewed by participating pathologists. In set A (61 cases), participants were provided with hematoxylin/eosin (HE)-stained sections. In set B (62 cases), participants were provided with HE-stained sections and E-cadherin immunohistochemistry (IHC). Tumor characteristics were balanced. Participants classified specimens as non-lobular BC versus mixed BC versus ILC. Pairwise inter-observer agreement and agreement with a pre-defined reference diagnosis were determined with Cohen's kappa statistics. Subtype calls were correlated with molecular features, including CDH1/E-cadherin mutation status. Thirty-five pathologists completed both sets, providing 4,305 subtype calls. Pairwise inter-observer agreement was moderate in set A (median κ = 0.58, interquartile range [IQR]: 0.48-0.66) and substantial in set B (median κ = 0.75, IQR: 0.56-0.86, p < 0.001). Agreement with the reference diagnosis was substantial in set A (median κ = 0.67, IQR: 0.57-0.75) and almost perfect in set B (median κ = 0.86, IQR: 0.73-0.93, p < 0.001). The median frequency of CDH1/E-cadherin mutations in specimens classified as ILC was 65% in set A (IQR: 56-72%) and 73% in set B (IQR: 65-75%, p < 0.001). Cases with variable subtype calls included E-cadherin-positive ILCs harboring CDH1 missense mutations, and E-cadherin-negative ILCs with tubular elements and focal P-cadherin expression. ILCs with trabecular growth pattern were often misclassified as non-lobular BC in set A but not in set B. In conclusion, subtyping of BC as ILC achieves almost perfect agreement with a pre-defined reference standard, if assessment is supported by E-cadherin IHC. CDH1 missense mutations associated with preserved E-cadherin protein expression, E- to P-cadherin switching in ILC with tubular elements, and trabecular ILC were identified as potential sources of discordant classification.

Dataset Information

Relevance of systems biological approach in the differential diagnosis of invasive lobular carcinoma & invasive ductal carcinoma.

Publications

Relevance of systems biological approach in the differential diagnosis of invasive lobular carcinoma & invasive ductal carcinoma.

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