Clinicopathological features and prognosis of AFP-producing colorectal cancer: a single-center analysis of 20 cases

Abstract

Background: High serum levels of alpha-fetoprotein (AFP) are observed in some gastrointestinal cancers. However, primary AFP-producing colorectal cancer (CRC) is extremely rare and causes confusion among clinicians. In this study, we analyzed the clinicopathological features and clinical outcomes of AFP-producing CRC and provide a brief view of this rare carcinoma. Patients and methods: Twenty patients with AFP-producing CRC were enrolled at the Fudan University Shanghai Cancer Center from 2012 to 2015. Clinical information, including serum AFP and CEA levels, and outcomes were collected. Tumors were divided into three histologic types: the common adenocarcinoma (COM) type, mucinous adenocarcinoma type and hepatoid type (HPT). Immunohistochemical (IHC) staining of GPC3, Hepa-1, SALL4 and Arg-1 was performed. Additionally, mutations of the KRAS, NRAS and BRAF genes were examined. Finally, another 40 stage-matched patients with traditional CRC were enrolled as controls for survival analysis. Results: AFP-producing CRC was more likely to occur in males (60%) and arose mainly from the ascending (40%) and sigmoid (35%) colon. In addition, the majority of patients with AFP-producing CRC had poor differentiation (50%), advanced local invasion (80%) and lymph node (LN) metastasis (60%). Synchronous distant metastasis was commonly observed (35%). Interestingly, serum AFP levels were closely associated with LN metastasis. Histopathologically, the COM type was the most common pattern. In IHC staining, the HPT pattern was the most distinct due to high positivity rates of GPC3, Hepa-1 and Arg-1. One patient had mismatch repair deficiency, and another had a KRAS mutation. Patients with AFP-producing CRC had worse progression-free and overall survival than patients with traditional CRC. Conclusion: AFP-producing CRC has unique clinical and histopathological characteristics, showing an aggressive biological behavior and worse prognosis than traditional CRC.

Keywords: AFP-producing colorectal cancer; clinicopathological features; prognosis; serum AFP.

Figure 1

Statistical analysis of the serum AFP between different clinicopathological parameters. (A) The serum AFP levels in patients with LN metastasis were significantly higher than those in patients without LN metastasis. There were no significant differences between the AFP level and local invasion (T stage) (B), distance metastasis (C), or TNM stage (D). Abbreviations: LN, lymph node; NS, not significant.

Figure 2

(A) Poorly differentiated CRC composed of hepatoid type (HE, original magnification×200). (B) Types of histological transitions in AFP-producing CRC, transition from COM (right side) to HPT (left side) (HE, original magnification×40). (C–E) Immunohistochemical staining: (C) Hepa-1; (D) GPC-3; (E) Arg-1. (immunohistochemistry, original magnification×200). Abbreviations: COM, common adenocarcinoma type; CRC, colorectal cancer; HPT, hepatoid type.

Figure 3

Comparisons of immunohistochemical staining in different histological patterns. The positive staining rate of GPC3 (A), Hepa-1 (B) and Arg-1 (C) was significantly higher in the HPT than in the non-HPT. Abbreviation: HPT, hepatoid type.

Figure 4

Kaplan–Meier estimates of PFS (A) and OS (B) among patients with low serum AFP levels and high serum AFP levels. Kaplan–Meier estimates of PFS (C) and OS (D) among patients in the AFP-producing CRC and control groups. (P<0.05). Abbreviations: CRC, colorectal cancer; OS, overall survival; PFS, progression-free survival.