Imunohistokemijska izraženost NEDD9 i E-kadherina u bolesnika s metastatskim i nemetastatskim kolorektalnim karcinomima [Immunohistochemical expression of NEDD9 and E-Cadherin in Patients with Metastatic and Non-Metastatic Colorectal Carcinoma]

Jurčić, Petra (2017) Imunohistokemijska izraženost NEDD9 i E-kadherina u bolesnika s metastatskim i nemetastatskim kolorektalnim karcinomima [Immunohistochemical expression of NEDD9 and E-Cadherin in Patients with Metastatic and Non-Metastatic Colorectal Carcinoma]. PhD thesis, Sveučilište u Zagrebu.

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Abstract

Colorectal carcinoma (CRC) is a heterogeneous disease with different clinical presentation, molecular characteristics, response to treatment and survival prognosis. In patients with CRC, the loss of E-Cadherin expression and the higher expression of NEDD9 are considered as factors of worse prognosis. The aim of our study was to analyse immunohistochemical expression of NEDD9 and E-Cadherin as markers of metastatic potential. We have analysed the expression of NEDD9 and E-Cadherin in 51 samples of non-metastatic CRC, 50 samples of CRC with metastases in lymph nodes and 40 samples of CRC with liver metastases. The expression of NEDD9 and E-Cadherin was compared with the traditional prognostic factors (the size of the tumour, TNM stage, surgery margins, microscopic vascular invasion, perineural invasion, and the state of the lymph nodes, the age and sex of the patients at the time of diagnosis) as well. Significant differences in the intensity of reactions (P < 0,001) and immunohistochemical index of staining (P < 0,001) with regards to E-Cadherin staging in primary tumour were discovered. Significant differences between metastases in lymph nodes and liver metastates regarding the immunohistochemical staining of E-Cadherin were also discovered (P = 0,027). No significant differences in the expression of NEDD9 in CRC with or without metastases in lymph nodes and liver were discovered. In Dukes B and D tumours no significant correlation coefficients between the expression of NEDD9 and E-Cadherin and traditional prognostic factors were found. In Dukes C tumours, we found a significant positive correlation of E-Cadherin immunohistochemical staining index in primary tumour with regards to age (rho = 0,311, P = 0,028), and positive correlation of NEDD9 in primary tumour regarding the N classification (rho=0,307, P = 0,030), while a significant negative correlation was found between E-Cadherin immunohistochemical staining index in primary tumour regarding the size of tumour (rho = -0,289, P = 0,042). No significant differences in survival were found regarding the expression of E-Cadherin and NEDD9 in primary tumour, lymph node metastases, and liver metastases. Our results point to the potential role of determination of E-Cadherin and NEDD9 in primary tumour as metastatic markers, in patients with CRC that has metastasized in lymph nodes. Additionally, these discoveries could be useful for prescribing the correct treatment.

Abstract in Croatian

Kolorektalni karcinom je heterogena bolest s različitom kliničkom prezentacijom, molekularnim karakteristikama, odgovorom na liječenje i prognozom preživljenja. Smatra se da je gubitak izraženosti E-kadherina i pojačana izraženost NEDD9-a čimbenik lošije prognoze u bolesnika s kolorektalnim karcinomom. Cilj naše studije je bio ispitati imunohistokemijsku izraženost NEDD9-a i E-kadherina kao biljega metastatskog potencijala. Analizirana je izraženost NEDD9-a i E-kadherina u 51 uzorku kolorektalnog karcinoma koji nije metastazirao, 50 uzoraka kolorektalnog karcinoma s metastazama u limfne čvorove te 40 uzoraka kolorektalnog karcinoma s jetrenim metastazama. Dodatno je uspoređena izraženost NEDD9-a i E-kadherina s tradicionalnim prognostičkim čimbenicima (veličina tumora, TNM stadij, operacijski rubovi, mikroskopska vaskularna invazija, perineuralna invazija, status limfnih čvorova, dob i spol bolesnika u trenutku postavljanja dijagnoze). Zabilježene su značajne razlike u intenzitetu reakcije (P < 0,001) te imunohistokemijskom indeksu bojanja (P < 0,001) obzirom na stupnjevanje E-kadherina u primarnom tumoru te između metastaza u limfne čvorove i metastaza u jetra u imunohistokemijskom indeksu bojanja E-kadherina (P = 0,027). Nisu nađene značajne razlike u izraženosti NEDD9-a u kolorektalnim karcinomima s i bez metastaza u limfne čvorove i jetra. U podskupinama Dukes B i D nije bilo značajnih korelacijskih koeficijenata između izraženosti NEDD9-a i E-kadherina s tradicionalnim prognostičkim čimbenicima. U podskupini Dukes C značajne su pozitivne korelacije imunohistokemijskog indeksa bojanja E-kadherina u primarnom tumoru s dobi (rho = 0,311, P = 0,028) te NEDD9-a u primarnom tumoru s N klasifikacijom (rho = 0,307, P = 0,030) dok je značajna negativna korelacija zabilježena između imunohistokemijskog indeksa bojanja E-kadherina u primarnom tumoru s veličinom tumora (rho = -0,289, P = 0,042). Nije bilo značajnih razlika u preživljenju obzirom na izraženost E-kadherina te NEDD9-a u primarnom tumoru, metastazama u limfne čvorove kao ni u jetrenim metastazama. Naši rezultati ukazuju na potencijalnu ulogu određivanja izraženosti E-kadherina i NEDD9- a u primarnom tumoru kao metastatskih biljega u bolesnika s kolorektalnim karcinomom koji je metastazirao u limfne čvorove. Osim toga, ta saznanja bi mogla koristiti pri izboru liječenja.

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