Introduction 1 2 4 5 6 7 8 9 10 11 12 13 14 15 16 21 22 24 25 28 29 This study correlates CD24 and MAPK expression with patient survival in cholangiocarcinoma with the objective of identifying a subset of patients who may benefit from targeted molecular therapy. Patients and Methods Clinical Data After obtaining approval of the Institutional Review Board, a review of the tumor registry at Roswell Park Cancer Institute identified 31 consecutive patients with histologically proven cholangiocarcinoma between 1996 and 2002. Twenty-two patients had adequate tissue for further histopathologic studies and constitute the basis of this study. Medical records of these patients were reviewed for demographic data including age; gender; surveillance, epidemiology, and end results (SEER) stage at presentation; treatment; and survival from the time of diagnosis. Immunohistochemical Staining 2 2 30 \documentclass[12pt]{minimal}
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\begin{document}$$ {\left( {50 \times 1} \right)} + {\left( {30 \times 2} \right)} + {\left( {20 \times 3} \right)} = 170 $$\end{document} Histological Grading The cholangiocarcinoma tissue specimens were also stained by routine H&E stains. The specimens were graded based on the degree of tumor differentiation using the World Health Organization (WHO) system. Statistical Analysis Association between biomarker expressions in tumor tissue was investigated using the Kendall’s tau. Biomarker expressions were classified as high and low based on whether their scores were above or below the median value, and survival between low and high expressions was compared using the log-rank test. The Kaplan–Meier method was also used to estimate the survival curves and median survival. The Cox’s proportional hazards survival analysis was used in the multivariate analysis of survival data to explain the effect of biomarker expressions together with other diagnostic parameters. Patient demographics including age, tumor grade, SEER stage, and treatment received were considered as possible parameters for explanatory variables in the model. All statistical tests were two-sided with statistical significance level at 5%. Results Patient Characteristics n n n n n Immunohistochemical Staining 1 1 Figure 1 right upper corner  Relationship Between Biomarkers τ p Survival 2 3 p 4 p p p 1 Figure 2 n p  Figure 3 n p  Figure 4 n p  Table 1 Prognostic Variables for Survival in 22 Patients with Cholangiocarcinoma Variable n Median survival (months) p p Age <68 11 17 (8–36) 0.60  >68 11 11 (5–52)  Gender Male 7 12 (8–163) 0.52  Female 15 17 (6–52)  Grade 1, 2 12 15 (6–52) 0.99  3 10 11 (8–*)  SEER stage 1, 2 15 11 (6–52) 0.48  3 7 28 (6–163)  Chemotherapy No 10 6 (4–13) 0.0005 0.0014 Yes 12 52 (17–163) Radiation No 16 8 (6–28) 0.12  Yes 6 44 (17–*)  Surgery No 3 8 (0–28) 0.17  Yes 19 17 (7–52)  MAPK Low 10 17 (8–36) 0.68  High 11 28 (5–163)  P-MAPK Low 10 13 (8–52) 0.34  High 11 36 (4–163)  CD24 <120 9 36 (13–163) 0.10 0.02 >120 13 8 (6–28) *The estimate was not provided because the upper limit of the survival curve had not reached a 50% failure rate. CD denotes cluster of differentiation. p-MAPK denotes phosphorylated form of mitogen-activated protein kinase. Discussion 22 24 31 26 27 28 32 p 29 33 34 35 36 37 38 39 40 41 16 21 16 8 In conclusion, overexpression of the molecular marker CD24 in cholangiocarcinoma is predictive of poor survival. CD24 overexpressors demonstrated a lack of response to chemotherapy and possibly radiation therapy although these observations were limited by the small sample size. Additional properties of tumor proliferation, invasion, metastasis, and apoptosis make CD24 a potent target for specifically directed molecular therapy and its overexpression a potential criterion in the selection of patients for the appropriate conventional treatment modality.