A1 Refereed original research article in a scientific journal

Immunological tumor status may predict response to neoadjuvant chemotherapy and outcome after radical cystectomy in bladder cancer




AuthorsTervahartiala M, Taimen P, Mirtti T, Koskinen I, Ecke T, Jalkanen S, Bostrom PJ

PublisherNATURE PUBLISHING GROUP

Publication year2017

JournalScientific Reports

Journal name in sourceSCIENTIFIC REPORTS

Journal acronymSCI REP-UK

Article numberARTN 12682

Volume7

Number of pages9

ISSN2045-2322

eISSN2045-2322

DOIhttps://doi.org/10.1038/s41598-017-12892-5

Self-archived copy’s web addresshttps://research.utu.fi/converis/portal/detail/Publication/26892589


Abstract
Bladder cancer (BC) is the ninth most common cancer worldwide. Radical cystectomy (RC) with neoadjuvant chemotherapy (NAC) is recommended for muscle-invasive BC. The challenge of the neoadjuvant approach relates to challenges in selection of patients to chemotherapy that are likely to respond to the treatment. To date, there are no validated molecular markers or baseline clinical characteristics to identify these patients. Different inflammatory markers, including tumor associated macrophages with their plastic pro-tumorigenic and anti-tumorigenic functions, have extensively been under interests as potential prognostic and predictive biomarkers in different cancer types. In this immunohistochemical study we evaluated the predictive roles of three immunological markers, CD68, MAC387, and CLEVER-1, in response to NAC and outcome of BC. 41% of the patients had a complete response (pT0N0) to NAC. Basic clinicopathological variables did not predict response to NAC. In contrast, MAC387(+) cells and CLEVER-1(+) macrophages associated with poor NAC response, while CLEVER-1(+) vessels associated with more favourable response to NAC. Higher counts of CLEVER-1+ macrophages associated with poorer overall survival and CD68(+) macrophages seem to have an independent prognostic value in BC patients treated with NAC. Our findings point out that CD68, MAC387, and CLEVER-1 may be useful prognostic and predictive markers in BC.

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