Combined expression of HIF1α, VEGF and HER2 predicts metastasis, relapse and response to combination chemotherapy in colorectal cancer patients

• Published in: Annals of diagnostic pathology 2023-10, Vol.66, p.152168-152168, Article 152168
• Main Authors: Jamai, Dhouha, Kallel, Imen, Mekrazi, Saoussen, Aloulou, Samir, Walha, Marwa, Selmi, Boulbaba, Khabir, Abdelmajid
• Format: Article
• Language: English
• Subjects: Colorectal adenocarcinoma; FOLFOX-resistance; HER2; HIF1; Overall survival; Recurrence; VEGF
• ISSN: 1092-9134; 1532-8198
• DOI: 10.1016/j.anndiagpath.2023.152168

Addressing a single target is the frequent development of drug resistance followed by cancer relapse and treatment failure. Therefore, assessment of simultaneous expression of target molecules is essential to choose the optimal combination therapy for each colorectal cancer patient. This study aims to evaluate the immunohistochemical expression of HIF1α, HER2 and VEGF and to clarify their clinical significance as prognostic factors and predictive markers of FOLFOX (combination chemotherapy inclusive of Leucovorin calcium, Fluorouracil and Oxaliplatin response). Marker expression was retrospectively evaluated by immunohistochemistry in 111 patients with colorectal adenocarcinomas from south Tunisia, followed by statistical analysis. The immunohistochemical staining revealed that 45 %, 80.2 %, 86.5 % and 25.5 % of specimen were positive for nuclear, cytoplasmic HIF1α expression, VEGF and HER2 respectively. Nuclear HIF1α and VEGF were associated with worst prognosis while cytoplasmic HIF1α and HER2 were correlated with favourable prognosis. Multivariate analysis confirms the association between nuclear HIF1α, distant metastasis, relapse, FOLFOX response and 5 years overall survival. HIF1α positivity and HER2 negativity were significantly associated to short survival. Combined immunoprofiles HIF1α+/VEGF+, HIF1α+/HER2-, HIF1α+/VEGF+/HER2- were associated to distant metastasis, cancer relapse and short survival. Interestingly, our findings confirmed that patients bearing a HIF1α positive tumor were significantly more resistant to FOLFOX compared to negative ones (p = 0.002, p ≤ 0.001). Positive expression of HIF1α and VEGF, or decreased expression of HER2 was each associated with poor prognosis and short overall survival. In summary, we found that expression of nuclear HIF1α, alone or combined with VEGF and HER2 serves as a predictive marker of poor prognosis and FOLFOX response in colorectal cancer from south Tunisia. •Immunohistochemical expression of nuclear HIF1α, VEGF, COX-2, HER2 and prognostic value of each proteins were studied.•Nuclear HIF1α, VEGF, COX-2 and HER2 expression could be crucial indicator for overall survival of CRC patients.•Combined expression of nuclear HIF1α, VEGF, COX-2 and HER2 could independently predicts metastasis, relapse and overall survival of CRC patients from south Tunisia.