383

ARG1

arginase 1;ARG1;arginase 1

arginase, liver|arginase-1|liver-type arginase|type I arginase

6q23

protein-coding

BACKGROUND: Colorectal carcinoma (CRC) is one of the most common malignancies. In the current work, the role of arginase as a diagnostic marker in patients with recurrent CRC and colorectal liver metastases (CRCLM) was studied. METHODS: Arginase activity was monitored in serum from 40 patients with primary CRC and from 100 patients with CRCLM. Blood was taken before and after patients underwent tumor resection. Studies were conducted for 3 years. RESULTS: Preoperative arginase activity in serum from patients with CRC and CRCLM was much greater compared with the arginase activity in serum from healthy control blood donors. One and two cut-off levels of increased arginase activity were observed in patients with CRC and CRCLM, respectively. After patients underwent tumor resection, the arginase activity decreased to normal values in both patients with CRC and patients with CRCLM. Activity levels remained low in patients who did not develop recurrent CRC or CRCLM (first or second). In patients who developed subsequent recurrences or metastases that appeared after surgery, during 3 years of surveillance, a significant rise in serum arginase activity was observed. The clinical prognosis for patients was worst when the postoperative serum arginase activity was very high, because those patients more often developed second liver metastases or died. CONCLUSIONS: The authors conclude that the determination of serum arginase activity may be a complementary test to confirm the occurrence of CRC and may be useful for the early diagnosis of patients who develop recurrent CRC and/or CRCLM.

OBJECTIVE: The usefulness of simultaneous L-arginine and arginase determination in diagnosis of primary and metastatic colorectal cancer. METHODS: L-arginine and arginase were determined before and after surgery in serum from 43 patients with colorectal cancer (CRC), 24 with colorectal cancer liver metastasis (CRCLM), and 39 control subjects (10 patients with non-malignant diseases and 29 healthy blood donors). RESULTS: Preoperative L-arginine concentration in the patient groups was 2-fold higher, whereas arginase activity was over 3- and 6-fold higher in CRC and CRCLM when compared with control. The values of both parameters lowered significantly after surgery. The sensitivity of single parameter in CRC was 79% for L-arginine and 81% for arginase, and in CRCLM it was 83% for each parameter. The combination of L-arginine with arginase improved the sensitivity to 93% and 100% in CRC and CRCLM, respectively. The specificity of L-arginine and arginase calculated for 39 subjects was 87% and 82%. CONCLUSION: Simultaneous determination of L-arginine and arginase increases the value of arginase itself in diagnosis and follow up of patients with CRC and CRCLM.

The distinction of hepatocellular carcinoma (HCC) from metastatic tumor in the liver often presents a diagnostic challenge that carries significant impact on prognostication and therapy. The number of diagnostically useful immunohistochemical markers of hepatocytes is limited to hepatocyte paraffin antigen (HepPar-1), polyclonal carcinoembryonic antigen, and CD10, with alpha-fetoprotein and glypican-3 labeling HCCs. Arginase-1 (Arg-1) is a binuclear manganese metalloenzyme that catalyzes the hydrolysis of arginine to ornithine and urea. We used immunohistochemistry to compare the sensitivity of Arg-1 to that of HepPar-1 in 151 HCCs. We found that the overall sensitivities of Arg-1 and HepPar-1 are 96.0% and 84.1%, respectively. The sensitivities of Arg-1 in well, moderately, and poorly differentiated HCCs are 100%, 96.2%, and 85.7%, respectively, whereas, in comparison, HepPar-1 demonstrated sensitivities of 100%, 83.0%, and 46.4% for well, moderately, and poorly differentiated tumors, respectively. There were no HCCs in our study that were reactive for HepPar-1 but nonreactive for Arg-1. We also examined Arg-1 expression in nonhepatocellular tumors, including many that are potential mimics of HCC (renal cell carcinomas, neuroendocrine tumors, melanomas, gastric adenocarcinomas, and adrenocortical carcinomas) and found that only 2 non-HCC tumors were reactive for Arg-1. Arg-1 represents a sensitive and specific marker of benign and malignant hepatocytes that may ultimately prove to be a useful diagnostic tool in routine surgical pathology practice.

BACKGROUND: Arginase-I is a key urea cycle metalloenzyme that has been used as an immunohistochemistry (IHC) marker for hepatocellular carcinoma (HCC). Previous studies have demonstrated the efficacy of HepPar-1 and glypican-3 (GPC-3) IHC in liver fine needle aspiration (FNA) cytology. METHODS: Arginase-1 IHC was performed on FNA cell blocks, and its performance characteristics were compared with HepPar-1 and GPC-3. Ninety-two formalin-fixed, paraffin-embedded cell blocks were selected (HCC [n = 44], cirrhosis [n = 2], focal nodular hyperplasia [n = 3], hepatic adenomas [n = 2], dysplastic nodules [n = 6], and metastatic carcinomas [n = 35]). IHC staining with antibodies directed against arginase-1, HepPar-1, and GPC-3 was performed with appropriate positive and negative controls. RESULTS: Arginase-1 positivity was demonstrated in 37 of 44 (84.1%) cases of HCC, compared with 32 of 44 cases (72.7%) and 25 of 44 cases (56.8%) for HepPar-1 and GPC-3, respectively. Arginase-1 and GPC-3 expression were not observed in any cases of metastatic carcinoma (0%), whereas HepPar-1 expression was present in 1 case of metastatic carcinoma. In addition, both arginase-1 and HepPar-1 expression were present in all 13 cases (100%) of nonmalignant hepatocellular lesions, whereas GPC-3 expression was absent in all 13 cases (0%). CONCLUSION: This study demonstrates that both arginase-1 and HepPar-1 are effective IHC markers of hepatocellular differentiation. Furthermore, arginase-1 demonstrates superior sensitivity compared with GPC-3 and HepPar-1 in the diagnosis of HCC, whereas GPC-3 demonstrates superior specificity, as staining is not observed in benign hepatocellular lesions. Hence, use of arginase-1 with HepPar-1 and GPC-3 can aid in the diagnosis of HCC and separating from metastatic carcinoma.

BACKGROUND: The ability to distinguish hepatocellular carcinoma (HCC) from metastatic carcinoma (MC) involving the liver and cholangiocarcinoma (CC) by immunohistochemistry has been limited by the lack of a reliable positive marker for hepatocellular differentiation. Arginase-1 is a marker for HCC recently described in some literature. AIM: To examine the immunohistochemical staining of arginase-1 in cases of HCC, MC involving the liver and CC as compared to hepatocyte paraffin antigen -1 (HepPar-1) in an attempt to further define the diagnostic utility of arginase-1 in differentiating these tumors. MATERIALS AND METHODS: A comparative immunohistochemical study of arginase-1 and HepPar-1expression was performed in 50 HCC cases, 38 cases of MC to the liver from varying sites, 12 cases of CC and 10 specimens of normal liver tissues. The predictive capacity of arginase-1 and HepPar-1 staining was determined using sensitivity, specificity, positive predictive value, and negative predictive value calculations. RESULTS: All normal liver tissues (no=10), non- neoplastic cirrhotic liver tissues adjacent to HCC (no=42) as well as those adjacent to MC (no= 9) showed diffuse and strong immunostaining for both arginase-1 and HepPar-1. Arginase-1 demonstrated positive immunoreactivity in 42 of 50 (84%) cases of HCC compared with 35 of 50 (70%) for HepPar-1. Only one of 38 (2.6%) cases of MC and one of 12 (8.3%) cases of CC showed positive immunoreactivity for arginase-1. In contrast, HepPar-1 immunoreactivity was detected in 6 of 38 (15.8%) cases of MC and in 2 of 12 (16.7%) cases of CC. Arginase -1 showed a significantly higher sensitivity for HCC diagnosis (84%) compared to HepPar -1(70%) (p=0.016). The specificity of arginase-1 for HCC diagnosis was higher (96%) than that of HepPar -1 (84%); nevertheless, this was not statistically significant (p=0.109). Howerver, the combination of both immunomarkers for the diagnosis of HCC, raised the specificity to 100%. CONCLUSION: Arginase-1 immunostaining has a higher sensitivity and specificity than HepPar-1 for HCC diagnosis. Furthermore, the combined use of arginase-1 and HepPar-1 can provide a potentially promising tool to improve the accuracy in distinguishing HCC from metastatic carcinoma and cholangiocarcinoma. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9991436558072434.