Chromosome 17 polysomy: correlation with histological parameters and HER2NEU gene amplification

Area of Science:

• Oncology
• Genetics
• Pathology

Background:

• HER2NEU gene amplification is common in invasive breast carcinomas with HER2 protein overexpression.
• A subset of breast cancers exhibits polysomy 17, an increased copy number of chromosome 17.
• The clinical significance of polysomy 17 in breast cancer requires further investigation.

Purpose of the Study:

• To investigate the clinicopathologic significance of polysomy 17.
• To correlate polysomy 17 with histological parameters in breast cancer.
• To examine the relationship between polysomy 17 and HER2NEU gene amplification.

Main Methods:

• Surgical specimens from 266 primary invasive breast carcinomas were analyzed.
• HER2NEU gene status and CEP17 copy numbers were determined using fluorescent in situ hybridization (FISH).
• Polysomy 17 was defined as ≥3 average CEP17 signals per nucleus.

Main Results:

• Polysomy 17 was identified in 63 tumors (23.7%).
• Tumors with polysomy 17 showed adverse histological indicators: high histological and nuclear grade, poor Nottingham Prognostic Index, advanced local tumor extent, and progesterone receptor negativity.
• Polysomy 17 occurred in both HER2NEU amplified and unamplified tumors, being more frequent in unamplified cases (71.4%).

Conclusions:

• Polysomy 17 is associated with unfavorable prognostic factors in breast cancer.
• Polysomy 17 may contribute to HER2 protein overexpression in the absence of HER2 gene amplification.
• These findings suggest polysomy 17 as a potential mechanism for HER2 protein overexpression in specific breast cancer subsets.