Neuro-regulation of lower esophageal sphincter Predictive value of Ki67 and p53 in locally advanced rectal cancer: Correlation with thymidylate synthase and histopathological tumor regression after neoadjuvant 5-FU-based chemoradiotherapy

Abstract

AIM:To investigate the predictive value of Ki67 and p53 and their correlation with thymidylate synthase (TS) gene expression in a rectal cancer patient cohort treated according to a standardized recommended neoadjuvant treatment regimen. METHODS:Formalin fixed, paraffin embedded pretherapeutical tumor biopsies (n = 22) and posttherapeutical resection specimens (n = 40) from patients with rectal adenocarcinoma (clinical UICC stage Ⅱ/Ⅲ) receiving standardized neoadjuvant 5-fluorouracil (5-FU) based chemoradiotherapy were studied for Ki67 and p53 expression by immunohistochemistry and correlated with TS mRNA expression by quantitative TaqMan realtime PCR after laser microdissection. The results were compared with histopathological tumor regression according to a standardized semiquantitative score grading system. RESULTS:Responders (patients with high tumor regression) showed a significantly lower Ki67 expression than non-responders in the pre-therapeutical tumor biopsies (81.2% vs 16.7%; P < 0.05) as well as in the post-therapeutical resection specimens (75.8% vs 14.3%; P < 0.01). High TS mRNA expression was significantly correlated with a high Ki67 index and low TS mRNA expression was significantly correlated with a

A phase II study of neoadjuvant bevacizumab plus capecitabine and concomitant radiotherapy in patients with locally advanced rectal cancer

“…A significant correlation was observed of Ki-67 labeling index and RTA (P \ .0001) in agreement with the results by Jacob et al [29]. It appears plausible that the persistence of a fraction of high-proliferative cells in a larger RTA might be representative of resistant clones of cells and therefore, of a more aggressive phenotype.…”

Predictive Factors of Complete Response to Neoadjuvant Chemoradiotherapy in Patients with Rectal Cancer

“…Finally, high levels of TS are often associated with a high proliferating pattern (i.e. extensive Ki67 staining) [44,45]. Because highly proliferating tumors may be more susceptible to chemotherapy [46] and chemoradiotherapy [24], the positive predictive role of TS and Ki67 in our analysis might reflect a good response to a very active chemotherapy regimen by highly proliferating rectal tumors.…”

Tumor Markers of Neo-Adjuvant Chemo-Radiation Response in Rectal Cancer

“…The inclusion of p21 screening is warranted, as the referenced studies in (Salonga, Danenberg et al 2000), (Lenz, Danenberg et al 1998). Numerous studies assessing TS expression have found that pretreatment biopsies negative for TS were predictive of response (Saw, Morgan et al 2003), (Diez, Ramos et al 2003), (Jakob, Liersch et al 2008), (Negri, Campanini et al 2008). 3 studies revealed a better outcome with low or absent pretreatment TYMS expression, however another study demonstrated better outcome with high TYMS expression.…”

“…While it has been used as a prognostic factor for colorectal cancer, results have been inconclusive (Ogata, Greca et al), (Guzinska-Ustymowicz, Pryczynicz et al 2009), (Santagostino, Saggia et al 2007). A small number of independent studies have examined the levels of Ki67 positivity in pretreatment biopsies from rectal cancer patients (Kudrimoti, Lee et al 2007), (Debucquoy, Goethals et al 2006), (Tannapfel, Nusslein et al 1998), (Reerink, Karrenbeld et al 2004), (Rodel, Grabenbauer et al 2002), (Charara, Edmonston et al 2004), Some studies have shown a positive association with Ki67 index higher in responders compared to non responders (Kim, Park et al 2001;Jakob, Liersch et al 2008). The remaining studies showed no correlation between Ki67 status and patient outcome.…”