The Calcium Binding Protein Calretinin is a Selective Marker for Malignant Pleural Mesotheliomas of the Epithelial Type

Gotzos, V.; Vogt, Peter R.; Celio, Marco R.

doi:10.1016/s0344-0338(96)80208-1

Cited by 118 publications

(92 citation statements)

References 32 publications

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“…16,17 In 1996, Doglioni et al 16 reported strong calretinin expression in all 36 epithelioid mesotheliomas, but only focal staining was found in 28 (10%) of 294 adenocarcinomas of various origins and in 10 (18%) of 55 squamous carcinomas also of various origins. While many subsequent investigations have confirmed the usefulness of calretinin immunostaining in the differential diagnosis between mesotheliomas and lung adenocarcinomas, 8,[18][19][20][21][22][23][24][25][26][27][28][29] only a relatively few studies have been published on the expression of this marker in squamous carcinomas of the lung.…”

Section: Discussionmentioning

confidence: 99%

The diagnostic utility of immunohistochemistry in distinguishing between epithelioid mesotheliomas and squamous carcinomas of the lung: a comparative study

2006

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As both mesotheliomas and squamous carcinomas can present a wide variety of morphological patterns, they can on occasion be confused. Recently, some groups of investigators have called attention to the difficulties that sometimes exist in distinguishing between these malignancies and the need to define a panel of markers that can assist in reaching the correct diagnosis. The aim of the present study is to compare the value of the various immunohistochemical markers currently available for the diagnosis of mesothelioma and squamous carcinoma of the lung. A total of 30 epithelioid pleural mesotheliomas exhibiting a solid or predominantly solid pattern, and 30 nonkeratinizing squamous carcinomas of the lung were investigated for the expression of the following markers: podoplanin, calretinin, mesothelin, WT1, keratin 5/6, keratin 7, p63, carcinoembryonic antigen (CEA), MOC-31, Ber-EP4, B72.3, BG-8 (Lewis y ), leu-M1 (CD15), and thyroid transcription factor-1 (TTF-1). All 30 (100%) of the mesotheliomas reacted for calretinin, mesothelin and keratin 7, 93% each for podoplanin, WT1 and keratin 5/6, 13% for Ber-EP4, 7% each for p63, MOC-31 and BG-8, and 0% for B72.3, CEA, leu-M1 and TTF-1. All 30 (100%) of the squamous carcinomas were positive for p63 and keratin 5/6, 97% for MOC-31, 87% for Ber-EP4, 80% for BG-8, 77% for CEA, 57% for keratin 7, 40% for calretinin and B72.3, 30% for leu-M1, 27% for mesothelin, 15% for podoplanin, and 0% for WT 1 and TTF-1. After analyzing the results, it is concluded that from a practical point-of-view, a combination of two positive mesothelioma markers (WT1 and calretinin or mesothelin) with two negative mesothelioma markers (p63 and MOC-31) would allow the differential diagnosis to be established between epithelioid mesotheliomas and squamous carcinomas of the lung in nearly all instances.

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Section: Discussionmentioning

confidence: 99%

The diagnostic utility of immunohistochemistry in distinguishing between epithelioid mesotheliomas and squamous carcinomas of the lung: a comparative study

2006

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“…Calretinin is a 29-kDa protein that belongs to a family of calcium-binding proteins and that is strongly expressed in both neural tissues and certain non-neural cell types, including mesothelium (37). Its exact function is unknown, but it has been suggested that it is involved in the regulation of cell cycles (38).…”

Section: Discussionmentioning

confidence: 99%

Value of the Mesothelium-Associated Antibodies Thrombomodulin, Cytokeratin 5/6, Calretinin, and CD44H in Distinguishing Epithelioid Pleural Mesothelioma from Adenocarcinoma Metastatic to the Pleura

et al. 2000

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Until recently, the standard approach of most laboratories in distinguishing epithelioid pleural mesothelioma from metastatic adenocarcinoma has been a negative result from a panel of adenocarcinoma-associated antibodies. However, several "mesothelium-associated" antibodies have been proposed as useful in this situation, and we have applied four of these putative mesothelioma markers-thrombomodulin, cytokeratin 5/6, calretinin, and CD44H-to a series of 61 epithelioid pleural mesotheliomas and 63 metastatic adenocarcinomas with known primary sites (lung ‫؍‬ 19; breast ‫؍‬ 21; ovary ‫؍‬ 6; colon ‫؍‬ 10; kidney ‫؍‬ 4; uterus, epididymis, pancreas ‫؍‬ 1 case each). Of the mesotheliomas, 55 of 61 (90%) stained for thrombomodulin, 56 of 61 (92%) for cytokeratin 5/6, 47 of 51 cases (92%) were positive for calretinin, and 39 of 43 (91%) were positive for CD44H. Of the metastatic adenocarcinomas, 12 of 63 (19%) cases were positive for thrombomodulin, 9 of 63 (14%) were positive for CK5/6, and 27 of 60 (45%) were positive for CD44H. With calretinin, only 1 case of 59 (2%) showed positive nuclear staining. All four antibodies stained reactive mesothelium; thrombomodulin also stained endothelium; and CD44H variably stained lymphocytes, macrophages, and fibroblasts. We conclude that all four antibodies show high sensitivity for epithelioid mesothelioma, but only calretinin (98%), cytokeratin 5/6 (86%), and thrombomodulin (81%) show sufficient specificity for practical use in this situation.

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“…Aberrant CR expression occurs in certain colon cancer cell lines [Gotzos et al, 1996a] and in a majority of GIII colon tumors [Gotzos et al, 1999], but is also observed in almost all mesotheliomas of the epitheloid and the mixed type [Doglioni et al, 1996;Gotzos et al, 1996b]. Thus, we tested whether butyrate also affects proliferation of mesothelial and mesothelioma cells as well as CR expression levels in these cells.…”

Section: Butyrate Affects Survival Of Mesothelial and Mesothelioma Cementioning

confidence: 99%

“…The precise physiological role of CR in these cells is as yet unknown, but a role of CR in regulating neuron excitability and associated cerebellar function has been demonstrated before [Bearzatto et al, 2006]. Aberrant CR expression is observed in a majority of mesotheliomas of the epithelioid and mixed type [Doglioni et al, 1996;Gotzos et al, 1996b] and in a large proportion (>65%) of poorly differentiated (GIII) colon tumors [Gotzos et al, 1999]. Many colon cancer cell lines used as models to investigate tumorigenesis (e.g., WiDr), express high levels of CR [Gotzos et al, 1996a].…”

mentioning

confidence: 99%

A bipartite butyrate‐responsive element in the human calretinin (CALB2) promoter acts as a repressor in colon carcinoma cells but not in mesothelioma cells

Häner

Henzi

Pfefferli

et al. 2009

J of Cellular Biochemistry

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The short-chain fatty acid butyrate plays an essential role in colonic mucosa homeostasis through the capacity to block the cell cycle, regulate differentiation and to induce apoptosis. The beneficial effect of dietary fibers on preventing colon cancer is essentially mediated through butyrate, derived from luminal fermentation of fibers by intestinal bacteria. In epithelial cells of the colon, both in normal and colon cancer cells, the expression of several genes is positively or negatively regulated by butyrate likely through modulation of histone acetylation and thereby affecting the transcriptional activity of genes. Calretinin (CALB2) is a member of the EF-hand family of Ca 2þ -binding proteins and is expressed in a majority of poorly differentiated colon carcinoma and additionally in mesothelioma of the epithelioid and mixed type. Since CALB2 is one of the genes negatively regulated by butyrate in colon cancer cells and butyrate decreases calretinin protein expression levels in those cells, we investigated whether expression is regulated via putative butyrate-responsive elements (BRE) in the human CALB2 promoter. We identified two elements that act as butyrate-sensitive repressors in all colon cancer cell lines tested (CaCo-2, HT-29, Co-115/3). In contrast, in cells of mesothelial origin, MeT-5A and ZL34, the same two elements do not operate as butyrate-sensitive repressors and calretinin expression levels are insensitive to butyrate indicative of cell type-specific regulation of the CALB2 promoter. Calretinin expression in colon cancer cells is negatively regulated by butyrate via a bipartite BRE flanking the TATA box and this may be linked to butyrate's chemopreventive activity.

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The Calcium Binding Protein Calretinin is a Selective Marker for Malignant Pleural Mesotheliomas of the Epithelial Type

Cited by 118 publications

References 32 publications

The diagnostic utility of immunohistochemistry in distinguishing between epithelioid mesotheliomas and squamous carcinomas of the lung: a comparative study

The diagnostic utility of immunohistochemistry in distinguishing between epithelioid mesotheliomas and squamous carcinomas of the lung: a comparative study

Value of the Mesothelium-Associated Antibodies Thrombomodulin, Cytokeratin 5/6, Calretinin, and CD44H in Distinguishing Epithelioid Pleural Mesothelioma from Adenocarcinoma Metastatic to the Pleura

A bipartite butyrate‐responsive element in the human calretinin (CALB2) promoter acts as a repressor in colon carcinoma cells but not in mesothelioma cells

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