Future Perspectives

The search for new pathologic markers, different from the presently used morphologic ones, will increase the understanding of tumour biology, predictive rates and will improve therapies for each individual patient. In the absence of clear prognostic factors, oncologists may choose subjectively whether to perform surgery alone or to utilise adjuvant therapies. At present, tumour stage is still the most signif-

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Fig. 10a, b. Tumour regression assessment after pre-operative therapy: residual carcinoma. a Residual neoplastic gland. b Poorly differentiated pleomorphic tumour cells icant prognostic factor, but as tumours at the same stage may have different outcomes, new markers are needed to further subdivide tumours in term of prognostic and response to therapy.

Some of the genetic alterations identified in col-orectal carcinomas may be used as prognostic markers [91, 92]. Loss of chromosome 18q in stage II tumours (Dukes B) has been shown to be a good marker that predicts a high risk of metastasis and can be used to select tumours that will benefit from adjuvant chemotherapy [9]. High levels of microsatellite instability have been shown to be a positive prognostic marker, independent of stage [93, 94].

The absence of p27 expression seems to correlate with poor prognosis. None of the current markers can predict response to therapy, although selected molecular alterations may gain significance in the foreseeable future. Studies on colorectal tumour cell lines have shown that p53 status seems to have a role in the response to chemotherapy [95]. It has also been shown that MSI tumours are resistant to cis-platinum [96, 97] but sensitive to radiotherapy [98] and 5-FU [99]. Radio-sensitivity is related to p53, p21 mediated apoptosis; tumours without p53 mutations are more sensitive to radiotherapy [100]. Tumour stage and pTNM for resected patients are the most important prognostic factors that influence therapeutic strategies. While molecular markers are still not part of the staging system, they should be included in the pathology report whenever available.

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