Expression of p53 in adrenocortical tumours: clinicopathological correlations

McNicol, A. M.; Nolan, C.E.; Struthers, A. J.; Farquharson, M. A.; Hermans, J.; Haak, Harm R.

doi:10.1002/(sici)1096-9896(199702)181:2<146::aid-path744>3.3.co;2-z

Cited by 13 publications

(15 citation statements)

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“…The most frequently detected mutations in human malignancy involve the p53 tumor suppressor gene (25,26). Point mutations and/or deletions inactivate p53, allowing unchecked progression of cells containing damaged DNA through the S phase of the cell cycle, thereby supporting the development of a neoplastic phenotype (9,10,25,26). This and prior studies have demonstrated low to absent p53 immunoreactivity in adrenal adenomas; however, the rate of immunopositivity among carcinomas has been highly variable, ranging from 5% in this study to 52% (6,9,10,15).…”

Section: Discussionmentioning

confidence: 99%

Adrenocortical Adenoma and Carcinoma: Histopathological and Molecular Comparative Analysis

et al. 2003

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We compared histomorphological features and molecular expression profiles of adrenocortical adenomas (ACAd) and carcinomas (ACCa). A critical histopathological review (mean, 11 slides per patient) was conducted of 37 ACAd and 67 ACCa. Paraffinembedded tissue cores of ACAd (n ‫؍‬ 33) and ACCa (n ‫؍‬ 38) were arrayed in triplicate on tissue microarrays. Expression profiles of p53, mdm-2, p21, Bcl-2, cyclin D1, p27, and Ki-67 were investigated by immunohistochemistry and correlated with histopathology and patient outcome using standard statistical methodology. Median follow-up period was 5 years. Tumor necrosis, atypical mitoses, and >1 mitosis per 50 high-power fields were factors that were highly specific for ACCa (P < .001). Number (0 to 4) of unfavorable markers [Ki-67 (؉), p21 (؉), p27 (؉), mdm-2(؊)] expressed was significantly associated with mitotic activity and morphologic index (i.e., number of adverse morphologic features) and highly predictive of malignancy (P < .001). Ki-67 overexpression occurred in 0 ACAd and 36% ACCa (P < .001) and was significantly associated with mitotic rate and unfavorable morphologic index (P < .001). Tumor necrosis, atypical mitoses, >5 mitoses per 50 high-power fields, sinusoidal invasion, histologic index of >5, and presence of more than two unfavorable molecular markers were associated significantly with metastasis in ACCa. Wellestablished histopathologic criteria and Ki-67 can specifically distinguish ACCAd from ACCa. Tumor cell proliferation (Ki-67) correlates with mitotic activity and morphologic index. Tumor morphology is a better predictor of metastatic risk in ACCa than current immunohistochemistry-detected cell cycle regulatory and proliferation-associated proteins.KEY WORDS: Adenoma, Adrenal, Carcinoma, IHC, Tissue microarray. Mod Pathol 2003;16(8):742-751Adrenocortical carcinoma is a highly aggressive, rare endocrine malignancy. However, benign, clinically occult adrenal adenomas, adrenal "incidentalomas," are encountered frequently by abdominal imaging performed for unrelated indications. The unsuspected adrenal mass is detected in 2-4% of the general population and in Յ6% of abdominal computed tomography scans in patients aged 60 -70 years (1, 2). The size of the adrenal mass is considered to be the most reliable predictor of malignancy. As 8 -13.5% of resected adrenocortical carcinomas are Ͻ5 cm, size alone is an imperfect criterion for malignancy (3). In a study of metastasizing and nonmetastasizing adrenocortical tumors among 43 patients followed for a median of 11 years, Weiss (4) demonstrated the utility of nine histomorphologic criteria in predicting the biology of adrenocortical neoplasms. The histologic findings most predictive of malignancy were Ͼ5 mitoses per 50 high-power fields, atypical mitoses, and venous invasion. No single criterion could distinguish benign from malignant tumor biology; all but one of the benign adrenocortical tumors had two or fewer criteria. In a later study, Weiss et al. (5) modified the diagnostic criteria for benign and malig...

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Section: Discussionmentioning

confidence: 99%

Adrenocortical Adenoma and Carcinoma: Histopathological and Molecular Comparative Analysis

et al. 2003

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“…Flow cytometry has not offered diagnostic help in the evaluation of the malignant nature of the tumour (Cibas et al 1990, Padberg et al 1991, Medeiros & Weiss 1992. Proliferation marker Ki-67 and tumour suppressor gene p53 have been found helpful in distinguishing between adrenocortical adenomas and carcinomas (McNicol et al 1997, Nakazumi et al 1998. Abrogation of the MHC class II expression from adrenocortical tumours has been suggested to be a sign of the malignant nature of the tumour (Marx et al 1996).…”

Section: Introductionmentioning

confidence: 97%

Expression of inhibin alpha in adrenocortical tumours reflects the hormonal status of the neoplasm

Arola

Liu²,

Heikkilä³

et al. 2000

Journal of Endocrinology

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Inhibins are gonadal glycoprotein hormones whose main endocrine function is to inhibit pituitary FSH secretion. In addition to testes and ovaries, other steroid-producing organs are sites of inhibin subunit expression. To study the role of inhibins in human adrenal gland, we screened a panel of 150 adrenals (10 normal adrenals, 25 adrenocortical hyperplasias, 65 adrenocortical adenomas, 30 adrenocortical carcinomas and 20 phaeochromocytomas) for inhibin expression. mRNA levels of inhibin subunit were studied in 57 samples and all tissues were stained immunohistochemically with an inhibin subunit-specific antibody. Inhibin mRNA was detected in all adrenocortical tissues. Virilizing adenomas possessed a 10-fold higher median inhibin mRNA expression than did normal adrenals. Bilaterally and nodularly hyperplastic adrenals and other than virilizing adrenocortical tumours had their median inhibin mRNA levels close to those of normal adrenals. Immunohistochemically, inhibin subunit was detectable in all normal and hyperplastic adrenals, as well as in 73% of the adrenocortical tumours. However Our data show that inhibin subunit is highly expressed in both normal and neoplastic androgenproducing adrenocortical cells, with less expression in cortisol-producing and hardly any in aldosteroneproducing cells. This suggests a specific role for inhibins in the regulation of adrenal androgen production. We did not find any significant difference in inhibin expression between benign and malignant adrenocortical tumours. Thus inhibin gene does not seem to have a tumour suppressor role in human adrenal cortex.

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“…It also occurs more frequently in association with the Li-Fraumeni syndrome (Li and Fraumeni, 1969), associated with germline mutations of the p53 gene, on 17p13 (Srivastava et al, 1990). The demonstration of abnormal expression of IGF-II (Ilvesmaki et al, 1993) and p53 (Ohgaki et al, 1993;McNicol et al, 1997) in sporadic adrenocortical carcinoma would support a role for these proteins in tumorigenesis. The MEN-1 locus on chromosome 11q is another possible site of interest (Skogsaid et al, 1992;Iida et al, 1995).…”

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confidence: 71%

“…Potential candidates include p53 on 17p (McBride et al, 1986). We (McNicol et al, 1997) and others (Ohgaki et al, 1993) have shown altered p53 expression, most probably as a late event, in the development of adrenocortical carcinoma. There are two candidate loci on chromosome 18; DPC4 (deleted in pancreatic carcinoma) (Hahn et al, 1996) and DCC (deleted in colon cancer) (Vogelstein et al, 1988).…”

Section: Discussionmentioning

confidence: 99%

“…Since carcinomas are on average larger than adenomas, at present larger lesions are removed, while smaller ones are monitored. However, in view of the extremely poor prognosis of adrenocortical carcinoma with mortality up to 92% (Karakousis et al, 1985) it would be important to develop markers of malignant potential which could be applied to individual lesions at the earliest possible stage, as even small lesions may be malignant (McNicol, 1992). This might be made possible by identifying specific molecular genetic events differentiating neoplastic from hyperplastic nodules and indicating malignant potential.…”

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confidence: 99%

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Increasing genome instability in adrenocortical carcinoma progression with involvement of chromosomes 3, 9 and X at the adenoma stage

et al. 1999

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SummaryThe investigation of chromosomal aberrations in adrenocortical tumours has been limited by the difficulties of applying classical cytogenetics to tumours with low levels of proliferation. We have therefore applied the technique of interphase cytogenetics to paraffin-embedded archival specimens of 14 adrenocortical adenomas and 13 carcinomas. Hybridizations were performed using centromere-specific probes to chromosomes 3, 4, 9, 17, 18 and X, which have been shown to be altered in other types of tumours. Chromosomal imbalance was defined on the basis of changes in both chromosome index (CI) and signal distribution (SD). Where only one of these was altered, this was classified as a tendency to gain or loss. On the basis of the analysis of optimal hybridizations, carcinomas showed gains in all chromosomes studied, five of nine showing gains in multiple chromosomes. Gains were most common in chromosomes 3, 9 and, in particular X, eight of 11 showing gain, and one a tendency to gain. Chromosomal gain was seen less commonly in adenomas, but again chromosomes 3, 9 and X were involved. Losses were infrequent, only one carcinoma showing loss of chromosome 18, and adenomas showing a tendency to loss of chromosomes 4 (two cases), 17 (one case) and 18 (two cases). Our data suggest that changes in chromosomes 3, 9 and X are early events in adrenocortical tumorigenesis, and that there is increasing chromosomal instability with tumour progression.

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Expression of p53 in adrenocortical tumours: clinicopathological correlations

Cited by 13 publications

References 0 publications

Adrenocortical Adenoma and Carcinoma: Histopathological and Molecular Comparative Analysis

Adrenocortical Adenoma and Carcinoma: Histopathological and Molecular Comparative Analysis

Expression of inhibin alpha in adrenocortical tumours reflects the hormonal status of the neoplasm

Increasing genome instability in adrenocortical carcinoma progression with involvement of chromosomes 3, 9 and X at the adenoma stage

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