Subclonal analysis in a lobular breast cancer with classical and solid growth pattern mimicking a solid-papillary...

Area of Science:

• Oncology
• Genetics
• Pathology

Background:

• Invasive lobular breast cancer (ILBC) is the second most common type of breast cancer.
• A recently identified variant of ILBC exhibits a solid-papillary-like growth pattern.
• Understanding the molecular basis of ILBC variants is crucial for targeted therapies.

Purpose of the Study:

• To investigate the molecular characteristics of a case of ILBC with both solid-papillary-like and classical growth patterns.
• To determine the clonal relationship between the different histological components of the tumor.
• To confirm the existence and evolutionary origin of the solid-papillary-like ILBC variant.

Main Methods:

• Immunohistochemistry to assess protein expression (E-cadherin, beta-catenin).
• Gene expression profiling to classify tumor subtypes (luminal-A, luminal-B).
• Whole-genome copy number analysis and next-generation sequencing to identify genetic alterations (CNAs, CDH1 mutations).

Main Results:

• Both tumor components were ER/PR-positive, HER2-negative, and lacked E-cadherin/beta-catenin expression.
• Gene expression classified the main tumor as luminal-B and satellite foci as luminal-A.
• Shared CDH1 mutation and copy number alterations (1q gain, 16q loss) indicated common ancestry, with additional alterations in the main tumor (20q gain, 1p loss).

Conclusions:

• The study confirms the solid-papillary-like growth pattern variant of ILBC.
• Evidence suggests this variant arises from classical ILBC through subclonal evolution.
• Shared genetic alterations underscore the common origin of distinct histological patterns within the same tumor.