Immunohistochemical Detection of Metallothionein and MIB1 in Uterine Cervical Squamous Lesions

McCluggage, W. Glenn; Maxwell, Pamela; Bharucha, H.

doi:10.1097/00004347-199801000-00006

Cited by 26 publications

(27 citation statements)

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“…A similar observation was made for the proliferation-associated marker Ki67, where immunoreactive cells are characteristically dispersed throughout the entire epithelium of high-grade CIN. 11,12 NET-1/C4.8 therefore represents a unique marker that can differentiate between 2 entities of high-grade CIN on the basis of its expression pattern. Moreover, in contrast to p16 ink4 and Ki67, NET-1/C4.8 is not expressed in highly differentiated squamous cell cancers.…”

Section: Discussionmentioning

confidence: 99%

Identification of a new proliferation‐associated protein NET‐1/C4.8 characteristic for a subset of high‐grade cervical intraepithelial neoplasia and cervical carcinomas

Wollscheid

Kühne-Heid

Stein

et al. 2002

Intl Journal of Cancer

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A large number of genes are known to be differentially expressed at distinct steps of carcinogenesis. By using a cell culture model system for cervical cancer, we had previously identified several genes that were more strongly expressed when comparing normal cervical epithelium with cervical intraepithelial neoplasia (CIN) and cervical cancer. In our study, we show that one of these genes, C4.8, is identical to NET-1, which is a new member of the tetraspanin family of proteins. By generating a mouse polyclonal antiserum against the major extracellular domain of the protein, we could detect NET-1/C4.8 expression both after ectopic expression of the gene in cell cultures and in cryostat sections of cervical biopsies. Moreover, immunohistochemic analyses of normal cervical epithelium, metaplasia, condyloma and CIN of different severity suggest that NET-1/C4.8 expression is associated with neoplastic cell proliferation. Notably, expression of the protein throughout the entire epithelium is only evident for a subset of CIN3. The potential importance for this gene in cervical carcinogenesis is underlined by an invariably strong expression in all undifferentiated squamous cell cancers examined. This indicates that this gene may be of prognostic value.

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Section: Discussionmentioning

confidence: 99%

Identification of a new proliferation‐associated protein NET‐1/C4.8 characteristic for a subset of high‐grade cervical intraepithelial neoplasia and cervical carcinomas

Wollscheid

Kühne-Heid

Stein

et al. 2002

Intl Journal of Cancer

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“…This is in accord with the findings of Hishikawa et al (15) of a positive correlation between MT expression in squamous cell carcinoma of the oesophagus and staining for proliferative cell nuclear antigen. McCluggage and colleagues have also observed high MT expression in cervical lesions with high proliferative activity, namely Grade III cervical intra-epithelial neoplasms and invasive cervical squamous carcinoma (16). Bay and co-workers have reported higher levels of MT expression in the proliferative multiple layered epithelium of malignant serous and mucinous ovarian tumours compared with their benign counterparts (which have single epithelial layers) (10,17).…”

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confidence: 97%

Proliferative potential in nasopharyngeal carcinoma: correlations with metallothionein expression and tissue zinc levels

et al. 2000

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Metallothionein (MT) is a cysteine-rich protein with pleiotropic functions and a high binding affinity for heavy metals. The present study was designed to examine the relationship between MT expression and tissue zinc levels in conjunction with cell proliferation in nasopharyngeal cancer (NPC). Proliferative activity in NPC was quantified by Ki67 immunolabelling and MT expression was determined by immunohistochemistry. Total zinc and subcellular zinc fractions were analysed by flame atomic absorption spectrometry. MT immunostaining was observed in the nuclei of NPC cells, with the percentage MT immunopositivity ranging from 3.0 to 59.7%. Thirteen tumours displayed weak MT staining and the remaining 11 showed moderate to strong immunostaining. There was a significant positive correlation between MT and Ki67 positivity (P ⍧ 0.0127). Tissue zinc levels were higher in NPC as compared with benign nasopharyngeal tissues (4.800 ⍨ 0.4610 versus 2.889 ⍨ 0.4045 µg/g dry wt tissue, respectively; P ⍧ 0.0122). Nuclear zinc levels in NPC were significantly higher than levels in membrane and cytosolic fractions (mean zinc levels 1.4840 ⍨ 0.1489, 0.6286 ⍨ 0.0789 and 0.3014 ⍨ 0.0250 µg/mg protein, respectively). A linear relationship was also observed between nuclear zinc levels and MT immunostaining (P ⍧ 0.0024) as well as with Ki67 immunopositivity (P ⍧ 0.0123). Our results show that MT and zinc are correlated with proliferative activity in NPC, providing further insights into the biology of this enigmatic and aggressive tumour.Metallothioneins (MTs) are a family of intracellular cysteinerich proteins involved in a variety of cellular processes (1-3). The pleiotropic physiological roles of MT include metalloregulatory functions in cell growth, differentiation, repair and protection against oxidative stress-induced injury and apoptosis (1,3,4). Cell proliferation is believed to be a putative function of MT as there have been reports indicating MT to be a cell cycle-dependent protein. MT-positive nuclei were observed to be present specifically in the S to G 2 M phases of the cell cycle of regenerating hepatocytes (5). A 2-to 3-fold increase in MT expression (quantitated by enzyme-linked immunosorbent Abbreviations: EGF, epidermal growth factor; MT, metallothionein; NPC, nasopharyngeal carcinoma.© Oxford University Press 1809 assay) was observed in proliferating human colonic HT-29 cells (6).The proliferative potential of MT has also been linked to zinc, a trace element which participates in the activity of a number of DNA and RNA polymerases (2,7,8). MT has a high binding affinity for zinc and Zn-MT has been hypothesized to play important roles in transmission and expression of genetic information, in response to signals for cell activation (2,8). Zinc ions are sequestered in the metal thiolate clusters of the metalloprotein (7). In this study, our aim was to investigate the relationship of MT and zinc with proliferative activity in undifferentiated nasopharyngeal carcinoma (NPC), a cancer which is common among the Chinese popul...

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“…[21][22][23] In normal cervical squamous mucosa, Ki-67 positive cells are found mainly in the parabasal layers and some in the basal layer. 24 In cervical SILs, the number of Ki-67 positive cells increased as the cell grading went from normal to low grade SIL (LSIL) to high grade SIL (HSIL). 24 In a recent report by Ohara et al the Ki-67 PI in conjunctival SCC and CIN was statistically higher than that in ptergium.…”

mentioning

confidence: 98%

“…24 In cervical SILs, the number of Ki-67 positive cells increased as the cell grading went from normal to low grade SIL (LSIL) to high grade SIL (HSIL). 24 In a recent report by Ohara et al the Ki-67 PI in conjunctival SCC and CIN was statistically higher than that in ptergium. 25 In our study, we adopted a nested polymerase chain reaction (PCR) based genechip method and a subsequent DNA sequencing analysis to determine multiple HPV types in nine CIN and eight non-CIN conjunctival mucosal samples.…”

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confidence: 98%

Increased Ki-67 proliferative index and absence of P16INK4 in CIN-HPV related pathogenic pathways different from cervical squamous intraepithelial lesion

Kuo

Chang²,

Hsiao³

et al. 2006

British Journal of Ophthalmology

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Immunohistochemical Detection of Metallothionein and MIB1 in Uterine Cervical Squamous Lesions

Cited by 26 publications

References 0 publications

Identification of a new proliferation‐associated protein NET‐1/C4.8 characteristic for a subset of high‐grade cervical intraepithelial neoplasia and cervical carcinomas

Identification of a new proliferation‐associated protein NET‐1/C4.8 characteristic for a subset of high‐grade cervical intraepithelial neoplasia and cervical carcinomas

Proliferative potential in nasopharyngeal carcinoma: correlations with metallothionein expression and tissue zinc levels

Increased Ki-67 proliferative index and absence of P16INK4 in CIN-HPV related pathogenic pathways different from cervical squamous intraepithelial lesion

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