Immunohistochemical expression of metallothionein in normal human colorectal mucosa, in adenomas and in adenocarcinomas and their associated metastases

Abstract

The immunohistochemical distribution pattern of metallothionein, a low molecular weight protein with strong affinity for divalent heavy metal ions, has been investigated in normal and neoplastic conditions of the large bowel. Utilizing a monoclonal mouse antibody the following formalin-fixed paraffin-embedded surgical or biopsy samples were studied: tubulo-villous adenomas (8 cases); adenocarcinomas with various degree of differentiation (85), nine of which were mucinous-type; synchronous tubular or tubulo-villous adenomas separate from carcinomas (30); transitional mucosa (45); metastases in lymph nodes (43); and distant metastases (45). Twenty biopsies from the right and left colon of 10 patients affected by irritable bowel syndrome were also analyzed. Normal colonic mucosa as well as transitional mucosa showed metallothionein immunopositivity in enterocytes at the luminal surface and crypts. Evident nuclear and cytoplasmic staining was encountered in tubulo-villous adenomas; the same reactivity was noted in the basal glandular component of colorectal carcinomas-synchronous adenomas, while less intense staining was noted in the apical villous portions. A variable metallothionein immunostaining was observed in adenocarcinomas (62.3%), in lymph node (55.8%) and distant hepatic (17.2%) and omental (43.8%) metastases, although it was not always concordant with that reported in the corresponding primary tumour. Whether the metallothionein positivity observed in normal and neoplastic cells is the result of expression of a stable form of the protein or an accumulation in the nucleus and cytoplasm remains to be clarified.

Expression of Metallothionein in Colorectal Cancers and Synchronous Liver Metastases

“…However, to date, only limited information is available regarding the role of MT in colorectal carcinoma patients [13, 14, 15]. Öfner et al [13]reported that only 24% of the patients with Dukes D colon carcinoma were positive for MT and almost a similar percentage (21%) of patients were found to be positive in our patients.…”

“…It was considered as an important mechanism during tumor progression and appears to be predominantly correlated with more advanced, highly malignant tumors [11, 12]. However, to date only limited information is available regarding the role of MT in the pathogenesis of colorectal cancer and drug resistance in colorectal cancer patients [13, 14, 15]. In the present study, we have investigated MT expression in primary colorectal tumors and their corresponding liver metastatic lesion by immunohistochemistry, and have addressed whether MT expression at these two sites could affect the prognosis and drug resistance potential with regard to cisplatin.…”

Significance of overexpression of metallothionein in mouse urinary bladder focal lesions induced by treatment with N‐butyl‐N‐(4‐hydroxybutyl)‐nitrosamine

“…4) In humans, functional MT isoforms are encoded by 10 genes, 11) and their induction has been shown to be specifically regulated in a cell type-dependent manner. 12,13) Recently, MT has been detected in various types of human tumors, including breast, 14) urinary bladder, 15) testis, 16) salivary gland, 17) pancreas, 18) colon, 19) liver, 20) etc. Since it is very difficult to assess the significance of MT in urinary bladder carcinogenesis using tumor samples, we focused here on both early and late lesions induced with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) treatment in C57BL/6 mice.…”

Role of metallothionein in cisplatin sensitivity of germ-cell tumours

“…In our study, particularly, most of the non-responding tumours (75%) also showed over-expression of MT protein. Published data and results from the present study showed low levels of MT-protein expression in colon carcinomas, especially when compared with normal colon tissue (Guiffrè et al, 1996). Most interestingly, all post-chemotherapy residual vital germ-cell tumours tested showed a decreased or still undetectable level of MT-protein expression compared with their primary tumours.…”