ALDH1 expression predicts outcome in node-negative rectal cancer

Expression of the cancer stem cell marker aldehyde dehydrogenase 1 (ALDH1) is an independent predictor for poor prognosis in node-negative rectal cancer, researchers say.

As well as being associated with shorter survival, the results suggest that ALDH1 expression in rectal cancer cells may predict resistance to chemotherapy and radiotherapy.

"It is tempting to speculate that ALDH1 could disclose the tumors in need of novel treatment approaches and careful surveillance," write Tuulia Avoranta (University of Turku, Finland) and colleagues.

The researchers analyzed 64 preoperative biopsies and 213 operative samples from patients with stage I-III rectal cancer. Of these 213 patients, 89 received short-course preoperative radiotherapy, 50 received long-course preoperative radiotherapy, with or without chemotherapy, and 74 received no treatment before surgery.

In the overall cohort, there was no significant relationship between ALDH1 expression and survival. However, subgroup analysis revealed that in patients with node-negative tumors, ALDH1 expression was significantly associated with shorter disease-free survival (DFS) and disease-specific survival (DSS).

Multivariate analysis showed ALDH1 expression was associated with a 3.4-fold increased risk for shorter DFS and a 4.4-fold increased risk for shorter DSS compared with no ALDH1 expression.

Analysis of samples from 64 patients who had both preoperative and operative samples available, showed that after (chemo)radiotherapy, ALDH1 expression increased in 20% of pairs and 75% showed stable expression.

Additionally, tumors treated with a short or long course of radiation showed greater ALDH1 positivity than tumors without presurgical treatment (71 and 85 vs 63%, respectively).

These findings support the idea that ALDH1 positivity is related to resistance to radiotherapy, say the authors.

ALDH1-positive cancer cells exhibit properties such as in vitro self-renewal, multidrug resistance, expression of stem cell markers, and in vivo tumor initiation, explain Avoranta and colleagues. However, exploration of the association between the marker's expression and prognosis in colorectal cancer has led to conflicting results.

The authors say theirs is the first study specifically in rectal cancer and their findings could lead to a much needed new prognostic tool for the early stages of the disease.

"Our findings are of importance, because the criteria of giving adjuvant treatment especially stage II [colorectal cancer] are not unanimous, and accordingly, new prognostic biomarkers are needed," they write in Human Pathology.

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