Prognostic significance of alpha‐1‐antitrypsin in early stage of colorectal carcinomas

Abstract

We have previously shown that human colorectal carcinoma cell lines, RCM-1 and CoCM-1, synthesize alpha-1-antitrypsin (alpha 1-AT) in culture. We have studied immunohistochemically the incidence of alpha 1-AT on histologic sections from paraffin-embedded tissues of surgically resected colorectal carcinomas and their metastatic foci, polypectomized adenomas, and normal mucosae. alpha 1-AT was detected in 89 (61%) of 145 carcinomas (including 14 carcinomas in adenoma), and 12 (39%) of 31 adenomas. But only 2 (4%) of 55 normal colorectal mucosae were positive for alpha 1-AT. In metastatic tumor cells of colorectal carcinomas in lymph nodes and other organs, alpha 1-AT positivity was 60% and 82%, respectively. The incidence of alpha 1-AT was markedly higher in advanced adenocarcinomas than in early ones and more frequent in adenocarcinomas of right side (including transverse colon) than those of left side and rectum, regardless of their histological malignancy grades. In mucinous carcinomas the frequency was greater (8 of 9 cases) than in conventional adenocarcinomas. Clinical follow-up of the patients with colorectal carcinomas suggested that alpha 1-AT positivity in Dukes' stage A/B tends to correlate with unfavorable prognosis irrespective of the grade of histologic differentiation of carcinoma, but there is no significant relation in Dukes' stage C/D. Our findings suggest that alpha 1-AT in colorectal carcinoma is related to the invasive and metastatic capacity. It may thus serve as a biologic marker for prognosis of colorectal carcinomas at relatively early stages (Dukes' stage A/B).

Serpin Peptidase Inhibitor Clade A Member 1 (SerpinA1) Is a Novel Biomarker for Progression of Cutaneous Squamous Cell Carcinoma

“…7,8 Among the members of the serpin family, SerpinA1 and SerpinA3 have been reported to be overexpressed in various malignant tumors. High expression of the SerpinA1 gene has been found in papillary thyroid cancer, 29,30 lung and prostate cancer, 14,31 and colorectal adenocarcinoma. 15 In a recent study, SerpinA1 was among 129 genes whose elevated expression was associated with progression of esophageal squamous dysplasia.…”

“…12 Elevated expression of AAT is associated with the invasive and metastatic potential and poor prognosis in lung, colorectal, and gastric carcinoma. [13][14][15][16] In addition, ACT is expressed at high levels in gastric and salivary gland cancer and in malignant melanoma. 16 -18 Herein, we examined Serpin expression in cutaneous SCCs.…”

Serpin A1 is overexpressed in ALK+ anaplastic large cell lymphoma and its expression correlates with extranodal dissemination

“…[11][12][13] The levels of serpin A1 expression also appear to be correlated with the invasive and metastatic capacity of different tumor cells. 13,14 . The mechanisms by which serpin A1 could have this tumor and/or invasionpromoting effect remain unclear.…”

“…10 The prognostic significance of serpin A1 expression has been studied mainly in various adenocarcinomas. [11][12][13] In colorectal and lung adenocarcinomas, the level of serpin A1 expression is related to the invasive and metastatic capacity of tumor cells. 13,14 Clinical studies of patients with gastric and lung adenocarcinoma showed that strongly serpin A1-positive cases have poorer prognosis than weakly to moderately serpin A1-positive or serpin A1-negative cases.…”

“…[11][12][13] In colorectal and lung adenocarcinomas, the level of serpin A1 expression is related to the invasive and metastatic capacity of tumor cells. 13,14 Clinical studies of patients with gastric and lung adenocarcinoma showed that strongly serpin A1-positive cases have poorer prognosis than weakly to moderately serpin A1-positive or serpin A1-negative cases. 11,12 In a previous study using the suppression subtractive hybridization (SSH) technique to compare the gene expression between an ALK þ ALCL cell line and a clinical case of ALK À ALCL, we found that the serpin A1 gene was overexpressed in the ALK þ ALCL cell line.…”