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Meta-Analysis
. 2012 Nov;41(8):1195-205.
doi: 10.1097/MPA.0b013e3182580fb4.

Genetic markers of malignant transformation in intraductal papillary mucinous neoplasm of the pancreas: a meta-analysis

Sahar Nissim  1 , Gregory E Idos, Bechien Wu
Affiliations
Meta-Analysis

Genetic markers of malignant transformation in intraductal papillary mucinous neoplasm of the pancreas: a meta-analysis

Sahar Nissim et al. Pancreas. 2012 Nov.

Abstract

Objectives: The objective of this study was to determine the relationship between specific genetic alterations and malignant transformation in intraductal papillary mucinous neoplasm (IPMN) of the pancreas.

Methods: Quantitative meta-analysis was conducted of studies through October 2010 that adhered to the 1996 World Health Organization guidelines for distinguishing adenoma and borderline IPMN versus carcinoma in surgically resected specimens using a random-effects model. We developed a 6-point scoring system to assess study quality.

Results: Thirty-nine studies (1235 IPMN samples) satisfied the inclusion criteria, and we conducted pooled analysis of 8 genetic markers: MUC1, MUC2, MUC5AC, kRas, p53, hTERT (human telomerase reverse transcriptase), cyclooxygenase 2, and Shh (Sonic hedgehog). Markers having the strongest association with malignant IPMN were hTERT (odds ratio [OR], 11.4; 95% confidence interval [CI], 3.5-36.7) and Shh (OR, 6.9; 95% CI, 2.4-20.2), whereas MUC5AC (OR, 1.0; 95% CI, 0.1-13.9) and kRas (OR, 2.0; 95% CI, 1.0-4.3) showed weak association with IPMN histologic progression.

Conclusions: Expression of hTERT is strongly associated with malignant transformation in IPMN, consistent with up-regulation of hTERT as a key step in progression of IPMN to cancer. Expression of kRas and MUC5AC is common but not strongly associated with IPMN histologic progression. The quality criteria used here may guide future reporting of genetic markers related to malignant transformation of IPMN.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

FIGURE 1
FIGURE 1
Methodology used in this meta-analysis. A, We developed a 6-point scoring system to assess quality of studies based on recommendations from the STROBE and PRAISE guidelines. B, Flow diagram of the literature search and study selection.
FIGURE 2
FIGURE 2
Forest plot of studies examining association of MUC1 (A), MUC2 (B), or MUC5AC (C) expression and malignant transformation of IPMN. Methodologic quality of each study was assigned a score from 1 to 6 based on criteria summarized in Table 1. For each study, the quality score, OR; 95% CI, and relative weight are shown. The size of the data markers (squares) represents the statistical weight that each study contributed to the random-effects summary estimates; horizontal lines represent the 95% CI. The diamonds indicate the summary OR. I2 test P values evaluating study heterogeneity are shown.
FIGURE 3
FIGURE 3
Forest plot of studies examining association of kRas expression and malignant transformation of IPMN.
FIGURE 4
FIGURE 4
Forest plot of studies examining association of altered p53 expression and malignant transformation of IPMN.
FIGURE 5
FIGURE 5
Forest plot of studies examining association of hTERT (A), Cox2 (B), or Shh (C) expression and malignant transformation of IPMN.
FIGURE 6
FIGURE 6
A model for genetic alterations associated with malignant progression of IPMN based on the findings of this meta-analysis.
See this image and copyright information in PMC

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