RAS mutations vary between lesions in synchronous primary colorectal cancer: testing only one lesion is not sufficient to guide anti-EGFR treatment decisions.

INTRODUCTION: Mutations in KRAS and NRAS genes are negative predictors of anti-EGFR therapies response in metastatic colorectal cancer. There are few reports on RAS testing in synchronous primary colorectal cancer (SP-CRC) and a lack of recommendations on which tissue should be tested for the mutation in this disease. This study analyzed the RAS status of both lesions in SP-CRC patients and in their metastasis. MATERIALS AND METHODS: DNA was obtained from formalin-fixed-paraffin-embedded tissue, and mutations were analyzed by pyrosequencing. RESULTS: RAS status was heterogeneous in 6 (75%) of 8 SP-CRC patients between primary lesions. Five showed heterogeneity regarding RAS mutational status, and from these, four presented with metastasis: 3 cases (75%) had WT metastatic tissue, and 1 case (25%) had mutated metastatic tissue. One patient showed divergence regarding RAS mutation type. DISCUSSION: RAS mutations vary significantly between SP-CRC lesions, and the status of the metastasis is unpredictable. Testing for RAS mutations in only 1 of the primary lesions can misguide clinical decisions and hind the predictive potential of anti-EGFR treatment. A more appropriate approach in metastatic SP-CRC is to test the metastatic tissue or both primary lesions for providing more accurate mutation scenery and support more assertive clinical decisions.

Effect of HeNe laser irradiation on extracellular matrix deposition and expression of cytokines and chemokines in paracoccidioidomycotic lesions.

Paracoccidioidomycosis is the most prevalent human mycosis in Latin America. Cutaneous lesions are extremely painful and sensitive, and current treatment with antifungal drugs is lengthy and may cause side effects to patients. In this perspective, the helium-neon (HeNe) laser emerges as a novel therapy form due to its ability to heal wounds without changing cell function. In this work, we evaluate the effects of HeNe laser irradiation on extracellular matrix deposition and expression of cytokines and chemokines in cutaneous lesions caused by experimental infection of Balb/c mice. Our results showed decreased levels of pro-inflammatory interleukin (IL)-17 and tumor necrosis factor-alpha, and of anti-inflammatory IL-10 cytokines in lesions exposed to HeNe laser irradiation. Chemokines CCL3 and CXCL10 showed decreased levels in laser-treated lesions, but no significant difference was observed in relation to CCL5 expression. We also detected decreased density of fibronectin and laminin in HeNe laser-treated lesions. Data presented herein support the validity of our previous results suggesting positive effects of HeNe laser in accelerating wound healing in this experimental model. We believe that HeNe laser is a new nonharmful strategy that may be used as adjuvant and/or alternative therapy for improving treatment of paracoccidioidomycotic lesions.