Comparative Evaluation of HER2 Overexpression in Breast Carcinoma Using Cell Blocks and Corresponding Formalin-Fixed Paraffin-Embedded Tissue Blocks: A Prospective Study.

Background: Breast cancer is one of the most common cancers among women in Nigeria. Human epidermal growth factor receptor 2 (HER2) is an important prognostic and predictive biomarker that guides targeted therapy. The tumour grade is an important prognostic factor and is also important in the treatment of patients. In a resource-limited setting, cell block cytology may serve as an alternative for initial biomarker assessment and also as an initial diagnostic tool for planning definitive management. The study aims to compare HER2 overexpression of breast carcinoma using cell blocks and corresponding paraffin wax-embedded (FFPE) tissue blocks and to evaluate the concordance between both methods. Methodology: This was a one-year prospective study involving 83 cases of breast carcinoma patients with both cell block and corresponding FFPE tissue specimens. HER2 immunohistochemistry was performed using the ASCO/CAP 2018 guideline. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated with 95% confidence intervals (CI). Concordance was assessed using Cohen's kappa statistic. McNemar's test was used for paired comparisons. Results: The mean age of the study participants was 43.1 ±13.1 years, with a peak age group of 40-49 years. IHC HER2 overexpression was done on both cell blocks and histological blocks. In cell blocks, HER2 expression showed 15 cases (18.1%), 65 cases (78.3%), 3 cases (3.6%) were positive, negative, and equivocal, respectively while from histologic tissues, 15 cases (18.1%), 63 cases (75.9%), 5 cases (6.0%) were also positive, negative and equivocal respectively. The overall concordance rate between the two methods was 93.5%, with concordance rates of 100% for HER2-positive cases, 96.9% for HER2-negative cases, and 60% for equivocal cases. Sensitivity and specificity of cell block HER2 assessment were 96.9% (95% CI: 82.9-99.9) and 100% (95% CI: 94.3-100.0), respectively. The PPV of HER2 assessment on cell block was 100.0% (95% CI: 78.2-100.0), and the NPV was 97.1% (95% CI: 89.9-99.6). The kappa coefficient for agreement was 0.935, indicating excellent agreement. McNemar's test showed no statistically significant difference (p = 0.480). Equivocal (2+) cases were included without FISH confirmation. Most of the cases were invasive ductal carcinoma (NST), accounting for 97.6% (81 cases). Conclusion: Cell block cytology demonstrates strong concordance with FFPE tissue for HER2 assessment and may serve as a reliable alternative for initial triaging in resource-limited settings, particularly where tissue is not readily feasible. However, confirmatory testing on tissue biopsy remains essential, particularly for equivocal cases.