Detection of CEA mRNA, p53 and AE1/AE3 in Haematoxylin-eosin-negative Lymph Nodes of Early-stage Non-small Cell Lung Cancer May Improve Veracity of N Staging and Indicate Prognosis

Abstract

Although the surgical-pathological classification can be considered the 'gold standard' of T-N staging, it could not provide satisfactory and accurate estimation of survival rates in early-stage non-small cell lung cancer (NSCLC). In our study, the expression of carcinoembryonic antigen (CEA), p53 and intracytoplasmic keratin (AE1/AE3) using haematoxylin-eosin (HE) staining negative lymph nodes (LNs) in 28 patients with early-stage NSCLC were analysed using fluorescent quantitation reverse transcription-polymerase chain reaction (FQ-PCR) and immunohistochemistry (IHC). One hundred and ninety-three LNs were analysed. Two patients staged as I up-staged to II, and six patients staged as II up-staged to III. About 32, 19 and 36 LNs were positive, respectively, for CEA mRNA (32/193, 16.6%), p53 (19/193, 9.84%) and AE1/AE3 (36/193, 18.65%) compared with control LNs. Only FQ-PCR test for CEA mRNA could detect micrometastases in stage I NSCLC patients with N0 LNs (2/13, 15.4%). Disease-free time in patients with CEA mRNA (P = 0.000), p53 protein (P = 0.013) and AE1/AE3 (P = 0.003) positive were significantly inferior to those with micrometastases negative. Moreover, the results demonstrated that the positive LNs for CEA mRNA (P = 0.028), p53 protein (P = 0.048) and AE1/AE3 (P = 0.007) were associated with the relapse time, respectively. However, Cox proportional hazards test showed that only clinical stage was the independent risk factor of relapse, and denied the correlation between micrometastases in LNs and recurrence. Detection of CEA mRNA, p53, AE1/AE3 in HE-negative LNs may improve veracity of N staging and predict its prognosis in patients with early-stage NSCLC. Furthermore, micrometastases in stage I may be performed by FQ-PCR more sensitive than IHC.