Colorectal cancer molecular subtypes by immunohistochemistry in a patient cohort from Nigeria.

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Abdulkareem, F B
Khramtsova, G
Adedokun, Babatunde
Rotimi, O
Abudu, K
Badmos, K
Ibraheem, A F
Khramtsov, A
Sveen, Lise
Hurley, Ian
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Journal of Clinical Oncology
Colorectal cancer (CRC) classificationusesclinico-pathological characteristics. However, patients with similar histologic features and tumor stages have different clinical outcomes and drug responses. Studies of CRCmolecular heterogeneity have used genome-wide gene-expression data to classifypatients into four consensus molecular subtypes (CMS), but the complexity of analysis has limited its use in practice. Methods: With IRB approval, tissue microarray (TMA) blocks were constructed, IHC was performed and semi-quantitative scores completed. For the MMR proteins, MLH1 (Pierce), MSH2 (LifeTechnologies), MSH6 (Novex), PMS2 (Pierce) antibodies were used. Three markers were selected from transcriptomic analysis for IHC: CDX2 (LifeTechnologies), HTR2B (LifeTechnologies), and ZEB1 (eBioscience). Ki-67 (DAKO) proliferation rate was used as anequivalent marker for β-catenin activation.The CMS1 subtype was first separated using MSI/MSS status. A panel of CDX2, HTR2B, and ZEB1was then used to distinguish between CMS4 and CMS2/CMS3 subtypes, while Ki-67 was used to separate CMS2 from CMS3 subtype. Results: Of the total evaluable 75 CRC cases(mean age 44.8 years (SD = 16.1), 38% were <40 years old, and 60% were males. Of tumors with data on tumor grade (n=66), 62% were well differentiated. 59 patients (79%) had MSS, and the remaining16(21%) had MSI (i.e. CMS1). 22 (29%) patients with increased ZEB1 and lower CDX2 expression were classified as CMS4. 37 (49%) displayed increased CDX2 and lower ZEB1 expression and were classified as CMS2 (n=24) or CMS3 (n=13). HTR2B was universally expressed, but a higher median HTR2B score of 3 was observed in CMS4 cases compared to 1 for other subtypes (p=0.0001). The CMS4 subtype was significantly more likely to occur among young patients (p<0.001): in patients < 40 years, 70% of patients were CMS4 subtype, while in patients > 40, 7% were CMS4 subtype. Of the left-sided cancers, only 5% were CMS1 subtype, while CMS1 composed 75% of right-sided cancers (p<0.001). Conclusions: Using TMAs and a panel of antibodies, we show an association of a poorer prognostic subtype (CMS4) with younger age at diagnosis. IHC-based classification and screening could be a cost effective prognostic and predictive tool for Nigerian reference laboratories.
DOI: 10.1200/JCO.2019.37.15_suppl.e15145 Journal of Clinical Oncology 37, no. 15_suppl