Clinicians are relying increasingly on molecular biomarker testing methods to guide treatment of colorectal cancer (CRC). In June’s Clinical Laboratory News, Zahra Shajani-Yi, PhD, NRCC and Mark A. Cervinski, PhD, DABCC, FAACC, summarize the molecular history of CRC and the biomarkers that help define the etiology, prognosis and treatment response of this disease.

CRC, if caught early, has high survival rates although early stage disease doesn’t always present with symptoms. About half of all patients develop metastasis, often in the liver. Chromosomal instability (CIN) is the most common pathway of tumor development, followed by microsatellite instability (MSI).

“Predictive biomarkers help direct therapy decisions by providing information on differences in treatment response in biomarker-positive patients compared to biomarker-negative patients. Molecular analysis of tumor tissue also provides treatment-independent prognostic information on outcomes such as overall survival (OS) time or progression-free survival time,” the authors observe. APC is the most common gene mutation found in CRC cases, followed by TP53 (48%–59%), KRAS (40%–45%), and PIK3CA (14%–18%). Many others can show mutations at lower frequencies.

National pathology and oncology groups in 2017 issued evidence-based guidelines on molecular biomarker testing of colorectal tumor tissue as an aid in directing treatment. In their article, Shajani-Yi and Cervinski, address recommendations on tumor tissue biomarkers NRAS, KRAS, BRAF, PIK3CA, PTEN, and mismatch repair (MMR) testing, and their respective abilities to determine CRC etiology, treatment, and prognosis.

To evaluate for Lynch syndrome risk, the most common hereditary cause of CRC, the recommendation is to conduct a BRAF p.V600 mutational analysis in deficient MMR tumors with loss of MLH1, one of four MMR genes. “While the treatment modalities for sporadic and Lynch syndrome tumors may not differ, identifying patients with Lynch syndrome still matters, as it is inherited in an autosomal dominant manner and increases the risk of endometrial, ovarian, gastric, and other cancers,” Shajani-Yi and Cervinski explain.

BRAF p.V600 (BRAF c.1799 [p.V600]) testing is also useful in determining prognosis for patients with colorectal carcinoma but not for predicting anti-EGFR inhibitor response in patients.

Another guideline statement recommends that CRC patients receive MMR testing, which can identify those at high risk for Lynch syndrome and also provide prognostic data for sporadic CRC.

Pick up the June issue of CLN to learn more about guideline recommendations for other potential CRC biomarkers.