to be screened for CRC underwent stool M2-PK testing followed by ... test was positive, giving detailed description for their clinico-pathological characteristics.
Clinico-pathological Characteristics of Patients with Positive Stool M2-PK Test, UKM Medical Center Experience. Hajhamad M[1], Raja Affendi Raja Ali[2], MA Zairul [1], Nur Afdzillah Rahman[1], FJ Ruhi[1], Sagap I[1] 1 Colorectal
Surgery Unit, Department of Surgery, 2Gastroenterology Unit, Department of Medicine, Universiti Kebangsaan Malaysia Medical Center, Malaysia.
Introduction Colorectal cancer (CRC) is one of the most common cancers worldwide. Different screening programs have been developed and are offered in various countries worldwide. Detection of M2 Pyruvate Kinase enzyme (M2-PK) in patient stool is an evolving promising methods in this field. Many studies showed high sensitivity of the test, but, specificity still the issue of concern. Aim To identify which patient might be false positive for M2-PK and what are the possible underlying conditions that can lead to false positive results.
A cross sectional diagnostic study was carried out at UKM medical center. Patients who, suspected or request to be screened for CRC underwent stool M2-PK testing followed by colonoscopic examination and histopathological and radiological evaluation carried on whenever applicable. Patients’ demographics and clinical characteristics were obtained from patients records. Particular focus was given to those whose M2-PK test was positive, giving detailed description for their clinico-pathological characteristics. Chart 1. Presenting symptoms CRC cancer PR bleed
No Presenting symptoms
Indication for M2-PK
Colonoscopy
CEA
CT scan
Histopathology
1
PR bleed
3
Altered bowel habits Altered bowel habits Altered bowel habits Altered bowel habits Altered bowel habits
Not elevated NA
Sigmoid colon cancer with lung metastasis. Transverse colon cancer, no metastasis. Descending colon cancer with LN metastasis. Sigmoid colon cancer with liver metastasis Rectosigmoid tumor, no metastasis NA
Adenocarcinoma
PR bleed
Tumor at sigmoid colon Tumor at transverse colon Tumor at descending colon Tumor at rectosigmoid junction Tumor at rectosigmoid junction Colitis
Elevated
2
Workup PR bleed Workup PR bleed TRO colon cancer TRO colon cancer TRO colon cancer TRO colon cancer TRO colon cancer
Ulcers at sigmoid and Elevated recto-sigmoid junction
Thickening of rectosigmoid colon, no metastasis.
Benign rectosigmoid ulcer
Symptomatic anemia Asymptomatic
TRO colon cancer Screening
Colitis
NA
NA
Chronic active colitis
Normal
NA
NA
NA
10 Asymptomatic
Screening
Polyp at rectosigmoid junction
NA
NA
Benign colonic polyp
4
20% 10%
5
50% 20%
6 7
8 9
Elevated Elevated Elevated
Adenocarcinoma Adenocarcinoma
Pathological characteristic of M2-PK positive Adenocarcinoma Colitis
Adenocarcinoma
10%
Adenocarcinoma Colitis
20%
50%
20%
Table 1 Clinico-Pathological characteristic of M2-PK positive patients
Total of seventy seven patients, 36 males (46.8%) and 41 females (53.2%), were recruited in the study. Sixty seven (87%) have had negative M2-PK test, ten(13%) were positive. Of those, 5 patients (6.5%) have CRC, true positive, the other five (6.5%), false positive, they either have had a normal colonoscopy (n=1), chronic active colitis (n=2), benign ulcer (n=1) and tubular adenoma (n=1) patient. The overall sensitivity and specificity were 100% and 92.9% respectively, while positive predictive value was 50% and negative predictive value was 100%.
M2-PK stool test is of high sensitivity (100%) value, specificity of the test was affected, in most cases, by chronic active inflammatory process (Colitis or ulceration) which, itself, leads to high proliferation of affected cells and consequently predispose for malignancy. Further studies with larger sample size are required to further evaluate factors that may lead to false positive results.
1. Hong 2013. Perspectives of Mass Colorectal Cancer Screening and Early Clinical Diagnosis. Journal of GHR, 2(5): 564-567. 2. Tonus C, Sellinger M, Koss K et al. 2009.The faecal tumour M2-PK screening test for invasive & pre-invasive colorectal cancer: estimated specificity& results as a function of age for a study population of 4854 volunteers. NOWOTWORY Journal of Oncology,(59), 2, 32e–37e. 3. S Yogesh M, M Naumann, Gerhard M et al. 2006.Prospective multicenter evaluation of fecal tumor pyruvate kinase type M2 (M2-PK) as a screening biomarker for colorectal neoplasia, Int. J. Cancer:(119), 2651–2656.