Heat shock protein 70 and HLA-DR molecules tissue expression

Lazaris, Andreas C.; Theodoropoulos, George; Davaris, P; Panoussopoulos, Dimitris; Nakopoulou, Lydia; Kittas, Christos; Golematis, B

doi:10.1007/bf02048033

Cited by 75 publications

(72 citation statements)

References 22 publications

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“…Patients with HLA-DR positive carcinomas showed significantly better overall survival than in patients with DR negative carcinomas, which is consistent with several other studies (Gutierrez et al, 1987;Norheim Andersen et al, 1993;Lazaris et al, 1995;Morita et al, 1995;Kunihiro et al, 1998). Quite surprisingly, stratified analyses of survival with respect to MSI status, differentiation, ploidi and tumour localisation disclosed that in MSS/MSI-L tumours, in tumours with aneuploid DNA pattern and in moderately differentiated tumours, strong HLA-DR expression turned out to be a marker for favourable prognosis ( Figure 3A,B,C).…”

Section: Discussionsupporting

confidence: 91%

“…The presence of an inflammatory reaction in the form of TIL is most frequently found in MSI-H carcinomas (Jass et al, 1998;Smyrk et al, 2001). No association was found between Dukes' stage and HLA-DR expression, which is consistent with previous studies (Lazaris et al, 1995;Kunihiro et al, 1998). The MSI-H tumour phenotype is caused by defects in the DNA mismatch repair machinery, and stretches of repetitive sequences are prone to mutations.…”

Section: Discussionsupporting

confidence: 89%

“…The MHC encodes for three classes of cell antigens: class I (HLA-A, -B, -C), class II (HLA-DR, -DQ, -DP) and class III (Klein and Sato, 2000). HLA-DR antigen expression is usually not present in the epithelium of the large bowel, but may be turned on in inflammatory disorders, such as ulcerative colitis (Rognum et al, 1987), Crohn's disease and in colorectal tumours (Rognum et al, 1983;Gutierrez et al, 1987;Norheim Andersen et al, 1993;Chang and Sohn, 1995;Lazaris et al, 1995;Morita et al, 1995;Kunihiro et al, 1998). HLA-DR antigen expression on tumour cells is a marker of good prognosis in large bowel carcinomas (Gutierrez et al, 1987;Norheim Andersen et al, 1993;Lazaris et al, 1995;Morita et al, 1995;Kunihiro et al, 1998).…”

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Strong HLA-DR expression in microsatellite stable carcinomas of the large bowel is associated with good prognosis

et al. 2002

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Progression of colorectal cancer may follow either of two main genetic routes: the chromosome- or microsatellite-instability pathways. Association between the patients' prognosis and microsatellite instability has been questioned. Improved survival has previously been found in patients with expression of HLA-DR antigens on their tumour cells. In this study, the expression of HLA-DR antigen was investigated by immunohistochemistry in 357 large bowel carcinomas stratified by microsatellite instability status. Sixteen per cent of the tumours showed strong HLA-DR expression and 35% had weak DR expression. We confirmed that patients with strong positive HLA-DR staining had improved survival ( P <0.001) compared to patients with no HLA-DR expression. Strong epithelial HLA-DR staining was significantly associated with high level of microsatellite instability ( P <0.001). In the subgroup of tumours with characteristics typical of the chromosomal instability phenotype, i.e. in microsatellite-stable tumours, the patients positive for the HLA-DR determinants showed better survival than those without HLA-DR expression. The protective effect of HLA-DR expression on survival was confirmed by multivariate analysis, both in the whole patient group and in the microsatellite-stable/microsatellite instability-low group. This might be explained by enhanced T-cell mediated anti-tumour immune responses against tumour cells in the HLA-DR positive tumours. The finding of better patient survival in the subgroup of strong HLA-DR positive microsatellite-stable tumours may have clinical implications for these patients. British Journal of Cancer (2002) 87 , 756–762. doi: 10.1038/sj.bjc.6600507 www.bjcancer.com © 2002 Cancer Research UK

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 89%

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confidence: 99%

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Strong HLA-DR expression in microsatellite stable carcinomas of the large bowel is associated with good prognosis

et al. 2002

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“…24 Overexpression of HSP70 has been reported in various human tumors. [25][26][27][28][29] Overexpression of HSP70 also has been observed in cultured cells transformed with c-myc 30 or H-ras, 31 or cotransformed with H-ras/p53, 32 suggesting involvement of HSP70 in transformation or progression. Although many reports have described HSP70 expression in hepatoma cell lines, 33 to our knowledge, there have been no descriptions of HSP70 overexpression in human HCC tissues except for recent reports by Iizuka,34 who listed examples of HSP70 upregulation in human HCC tissues in microarray studies, and by Yin, 35 who described overexpression of HSP70 in HCC.…”

Section: Discussionmentioning

confidence: 99%

Expression profiling in multistage hepatocarcinogenesis: Identification of HSP70 as a molecular marker of early hepatocellular carcinoma

et al. 2003

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Hepatocellular carcinoma (HCC) associated with chronic liver disease evolves from precancerous lesions and early HCC to a progressed form. Nodule-in-nodule-type HCC (progressed HCC within early HCC) represents the transition from early to progressed HCC and, therefore, is useful in molecular genetic analysis of HCC progression during multistage carcinogenesis. We compared expression profiles among 7 early components and 7 progressed components of nodule-in-nodule-type HCCs and their corresponding noncancerous liver tissues with oligonucleotide array. Of the approximately 12,600 genes that were analyzed, a set of 95 genes provided a molecular signature that distinguished between early HCC components and their noncancerous liver tissues, and a set of 92 genes distinguished between progressed and early HCC components. Of these genes, the most abundantly up-regulated gene in early HCC components (P < .001) was heat-shock protein 70 (HSP70). Real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) confirmed this finding. Further immunohistochemical examination of HSP70 revealed its significant overexpression in early HCC compared with precancerous lesions (P < .001) and in progressed HCC compared with early HCC (P < .001). In conclusion, molecular signatures were clearly different in noncancerous liver tissue as compared with the early and progressed components of nodule-in-nodule-type HCC. Moreover, HSP70 could be a sensitive marker for the differential diagnosis of early HCC from precancerous lesion or noncancerous liver, a difficult distinction for pathologists due to very well differentiated histology with little atypia in early HCC. (HEPATOLOGY 2003;37:198-207.) H epatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide and one of the leading causes of cancer death in Japan. 1 Despite remarkable advances in diagnostic and therapeutic techniques, the incidence of HCC is still on the increase. HCC occurs mainly in livers that are chronically diseased as a result of hepatitis virus infection. 2 Progression often leads to vascular invasion and intrahepatic metastasis. As is known for other cancers, 3 HCC is also characterized by an obvious multistage process of tumor progression. Histopathologic and molecular biological studies have revealed the multistep development of human HCCs. [4][5][6][7] It has been shown that small nodular hypercellular lesions known as adenomatous hyperplasia (AH) or atypical AH (AAH: AH with focally increased atypia but too indefinite for a diagnosis of HCC) appear in damaged liver infected with hepatitis virus B or C. These lesions develop into early HCC, which corresponds to in situ or microinvasive carcinoma, in which the portal tracts within the nodule are preserved, and then into progressed HCC through the stage of nodule-in-nodule-type HCC (progressed HCC within early HCC), which indicates a transition from early to progressed HCC. These pathologic findings are also supported by radiologic findings. 8,9

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“…However, the available information about the prognostic significance of HLA class II antigen expression in cancers is conflicting (Table 3). While constitutive HLA class II antigen expression was reported to be associated with a favorable prognosis in some tumor types, e. g. CRC and larynx squamous cell carcinoma, [71][72][73][74] it was associated with higher metastatic dissemination, increased tumor stage and reduced patients' survival in other malignancies, such as melanoma and cervical carcinoma. [75][76][77] Conflicting is the information about the clinical relevance of HLA class II antigen expression in osteosarcoma; however, the number of tumors analyzed is too small to draw conclusions.…”

Section: Deregulation Of Hla Class II Apm Components In Malignant Cellsmentioning

confidence: 99%

HLA class II antigen-processing pathway in tumors: Molecular defects and clinical relevance

2017

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The human leukocyte antigen (HLA) class II antigen-processing machinery (APM) presents to cognate CD4 C T-cells antigenic peptides mainly generated from exogeneous proteins in the endocytic compartment. These CD4 C T cells exert helper function, but may also act as effector cells, thereby recognizing HLA class II antigen-expressing tumor cells. Thus, HLA class II antigen expression by tumor cells influences the tumor antigen (TA)-specific immune responses and, depending on the cancer type, the clinical course of the disease. Many types of human cancers express HLA class II antigens, although with marked differences in their frequency. Some types of cancer lack HLA class II antigen expression, which could be due to structural defects or deregulation affecting different components of the complex HLA class II APM and/or from lack of cytokine(s) in the tumor microenvironment. In this review, we have summarized the information about HLA class II antigen distribution in normal tissues, the structural organization of the HLA class II APM, their expression and regulation in malignant cells, the defects, which have been identified in malignant cells, and their functional and clinical relevance.

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Heat shock protein 70 and HLA-DR molecules tissue expression

Abstract: The resulting opposite effects on prognosis of examined markers seem to be related to different pathophysiologic functional roles on tumor immunology.

Cited by 75 publications

References 22 publications

Strong HLA-DR expression in microsatellite stable carcinomas of the large bowel is associated with good prognosis

Strong HLA-DR expression in microsatellite stable carcinomas of the large bowel is associated with good prognosis

Expression profiling in multistage hepatocarcinogenesis: Identification of HSP70 as a molecular marker of early hepatocellular carcinoma

HLA class II antigen-processing pathway in tumors: Molecular defects and clinical relevance

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