Integrating clinical, molecular, proteomic and histopathological data within the tissue context: Tissunomics

Abstract

Malignant tumors show a marked degree of morphological, molecular and proteomic heterogeneity. This variability is closely related to microenvironmental factors and the location of the tumor. The activation of genetic alterations is very tissue dependent and only few tumors have distinct genetic alterations. Importantly, the activation state of proteins and signaling factors is heterogeneous in the primary tumor and in metastases and recurrences. The molecular diagnosis based only in genetic alterations can drive to treatments with unpredictable responses depending on the tumor location such as the tumor response in melanomas vs. colon carcinomas with BRAF mutations.

Therefore, we understand that the correct evaluation of tumors requires a system that integrates both morphological, molecular and protein information in a clinical and pathological context, where intratumoral heterogeneity can be assessed. Then, we propose the term tissunomics where the diagnosis will be contextualized in each tumor based on the complementation of the pathological, molecular, protein expression, environmental cells and clinical data.

1.General background of tumour pathology.

2.Current situation and challenges.

Why are malignant tumours heterogeneous?.

Some oncogenic alterations are tissue‐specific.

Some histopathological features suggest oncogenic alterations.

3.Problems and barriers.

Bias and limitations of molecular classification and somatic theory.

Gene expression heterogeneity and environmental cells.

4.The solution: to integrate clinical, radiological, molecular and expression data in a tissue context.

5.Conclusions.

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