The role of the pathologist in tailored therapy

Konference: 2009 5. sympózium a workshop molekulární patologie a histo-cyto-chemie

Kategorie: Onkologická diagnostika

Téma: The role of the pathologist in the indication of the cancer treatment

Číslo abstraktu: 005

Autoři: prof. MUDr. Aleš Ryška, Ph.D.

The role of the pathologist has dramatically changed in recent decades. Originally, the main task of the (histo) pathologist was to establish the diagnosis of a tumor - including precise type of lesion, its biological potential, grade and stage. However, in certain cases the morphological classification of lesions did not correlate well with the biological potential of the tumor. Thus, the modern classification of tumors is based on a combination of morphology and the genetic profile of the neoplasm - this is also mirrored in the title of the new edition of WHO classification of tumors (Pathology and genetics of tumors).

Since the introduction of modern therapeutic options (biological treatment, individualized tailored" therapy), the original data supplied by the pathologist are not sufficient for clinicians (namely oncologists). They need and expect significantly more precise typing of the tumor, including detection of the expression of various molecules serving as targets for this advanced treatment.

Breast carcinoma may serve as a classical example - initially only detection of hormonal (estrogen and progesterone) receptors was needed for choice of appropriate treatment and estimation of prognosis. In recent years, the detection of HER-2/neu has been introduced and is now considered to be an integral part of pathological rating of such a tumor. In the course of time a system for external quality control for these examinations has been established, as validity and reproducibility are absolutely crucial for effective treatment.

New approaches to the treatment of colorectal cancer can serve as another example. After the introduction of an-ti-EGFR therapypathologists began to detect immunohistochemically EGFR in tumor cells. It was predicted that its expression would correlate with the effect of treatment as it had been observed in anti-HER-2/neu treatment of HER2 positive breast carcinomas. However, multiple studies have shown a lack of correlation of anti-EGFR therapy with immunohistochemical EGFR positivity.
A similar lack of correlation has also been found in the detection of a number of EGFR gene copies by fluorescent in situ hybridization (FISH). The proportion of patients who benefitted from treatment was virtually identical in EGFR positive and EGFR negative subgroups of patients with colorectal carcinoma. Recently, activating mutation of k-ras gene (observed in about 30% of all colorectal cancers) has been shown to be strongly associated with failure of the anti-EGFR therapy and molecular analysis of tumor DNA (search for most frequent mutations of k-ras gene) is now needed before starting this treatment.

These examples illustrate the need for deeper understanding of the molecular pathways involved in the etio-pathogenesis of cancer as well as in the mechanism of biological treatment. Thus, the pathologists will be more and more involved in the detection at various critical points (expression of proteins, mutations or rearrangements of genes, etc.) which may be responsible for success/failure of cancer treatment.

Datum přednesení příspěvku: 24. 4. 2009