Adrenal cortical carcinoma a study of 77 cases

Nader, Shahla; Hickey, Robert C.; Sellin, Rena V.; Samaan, Naguib A.

doi:10.1002/1097-0142(19830815)52:4<707::aid-cncr2820520424>3.0.co;2-n

Cited by 172 publications

(88 citation statements)

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“…18,19 Patient 2, with anaplastic thyroid carcinoma, was diagnosed at age 39 years; the average age of diagnosis for this tumor is 66.5 years. 20 The early age of onset for both of these patients is again highly suggestive that these tumors were related to the underlying MSH2 defect and not coincidental.…”

Section: Discussionmentioning

confidence: 99%

Unusual tumors associated with the hereditary nonpolyposis colorectal cancer syndrome

Broaddus

Lynch

et al. 2004

Modern Pathology

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The molecular pathogenesis of tumors outside the usual tumor spectrum for hereditary nonpolyposis colorectal cancer (HNPCC) is currently controversial. Specifically, it is not known whether these tumors are related to defects in DNA mismatch repair or arise independently of this defect in these patients. Here, we report two young patients, each with a known MSH2 mutation in the family, who developed rare tumors (adrenal cortical carcinoma and anaplastic carcinoma of the thyroid) that are not usually associated with HNPCC. Both of these patients were members of families that fulfilled modified Amsterdam (Amsterdam II) criteria for this familial cancer syndrome. Both the adrenal tumor and the thyroid tumor showed complete loss of immunohistochemical expression for MSH2 protein. Neither tumor was considered microsatellite instabilityhigh following microsatellite instability analysis using the established National Cancer Institute panel of five microsatellite markers. To our knowledge, MSH2 defects in these types of tumors have not been previously reported in patients with the HNPCC syndrome. Our results suggest that microsatellite instability analysis using the National Cancer Institute panel of five microsatellite markers may not detect microsatellite instability in tumors that fall outside the usual tumor spectrum of this syndrome. Therefore, when analyzing unusual tumors in patients with known or suspected HNPCC syndrome, we advocate the performance of immunohistochemistry for mismatch repair gene products in addition to microsatellite instability analysis.

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Section: Discussionmentioning

confidence: 99%

Unusual tumors associated with the hereditary nonpolyposis colorectal cancer syndrome

Broaddus

Lynch

et al. 2004

Modern Pathology

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“…This malignancy represents approximately 0.02% of all cancers (1,2) and within the general population occurs with a frequency of about two cases per million individuals per year (3). Nearly two-thirds of diagnosed patients are women.…”

Section: Introductionmentioning

confidence: 99%

Biosynthesis and metabolism of steroid hormones by human adrenal carcinomas

Brown

Fishman

2000

Braz J Med Biol Res

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Over a 15-year period, our university-based laboratory obtained 125 adrenal tumors, of which 15 (12%) were adrenal cortical carcinomas. Of these, 6 (40% of the carcinomas) occurred in patients with clear clinical manifestations of steroid hormone excess. Adrenal cortical carcinoma cells derived from the surgically resected tumors in 4 of these patients were isolated and established in primary culture. Radiotracer steroid interconversion studies were carried out with these cultures and also on mitochondria isolated from homogenized tissues. Large tumors had the lowest steroidogenic activities per weight, whereas small tumors had more moderately depressed enzyme activities relative to cells from normal glands. In incubations with pregnenolone as substrate, 1 mM metyrapone blocked the synthesis of corticosterone and cortisol and also the formation of aldosterone. Metyrapone inhibition was associated with a concomitant increase in the formation of androgens (androstenedione and testosterone) from pregnenolone. Administration of metyrapone in vivo before surgery in one patient resulted in a similar increase in plasma androstenedione, though plasma testosterone levels were not significantly affected. In cultures of two of four tumors examined, dibutyryl cAMP stimulated 11ß-hydroxylase activity modestly; ACTH also had a significant stimulatory effect in one of these tumors. Unlike results obtained with normal or adenomatous adrenal cortical tissues, mitochondria from carcinomatous cells showed a lack of support of either cholesterol side-chain cleavage enzyme complex or steroid 11ß-hydroxylase activity by Krebs cycle intermediates (10 mM isocitrate, succinate or malate). This finding is consistent with the concept that these carcinomas may tend to function predominantly in an anaerobic manner, rather than through the oxidation of Krebs cycle intermediates.

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“…6 Although early studies in the era before modern imaging modalities reported high response rates, it now is clear that mitotane has at best a 19 -22% response rate. [7][8][9] In addition to the evaluation of mitotane, numerous studies examining the efficacy of conventional chemotherapy have demonstrated either no or very low activity, indicating a limited role for these agents. 10 -12 Doxorubicin as a single agent or in combination chemotherapy has shown some activity against ACC.…”

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A phase II trial of combination chemotherapy and surgical resection for the treatment of metastatic adrenocortical carcinoma

Abraham

Bakke

Rutt

et al. 2002

Cancer

112

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BACKGROUNDAdrenocortical carcinoma (ACC) is rare, nearly always fatal, and to the authors' knowledge has few nonsurgical treatment options. Based on in vitro studies demonstrating the efficacy of mitotane as a P‐glycoprotein (Pgp) antagonist, and expression of high levels of Pgp in ACC, the authors conducted a study of infusional doxorubicin, vincristine, and etoposide with oral mitotane ± surgical resection in patients with metastatic ACC.METHODSThirty‐six patients with metastatic ACC received daily oral mitotane (mean, 4.6 g/day) and 96‐hour infusional doxorubicin (10 mg/m2/day), etoposide (75 mg/m2/day), and vincristine (0.4 mg/m2/day). Four responding patients (11%) underwent surgery.RESULTSThirty‐five patients were evaluable; all had metastatic disease. Eleven patients had not undergone resection of the primary tumor. Approximately 53% of patients had functional tumors. A total of 190 cycles were administered to 36 patients. Responses were observed in 8 patients (22%): 1 complete, 4 partial, and 3 minor responses. The mean duration of response was 12.4 months. Using a landmark method, the median survival of patients who did not respond to chemotherapy was 11.6 months from a point 4 months after the initiation of therapy, whereas that of 8 patients who demonstrated a response to chemotherapy was 34.3 months from that same landmark. High levels of Pgp expression were documented in nine of nine tumors. Mitotane levels > 10 μg/mL, previously shown to antagonize Pgp in vitro, were achieved in 25 of 36 patients (69%). However, rhodamine efflux from CD56‐positive cells was not impaired, suggesting poor in vivo Pgp inhibition. The predominant Grade 3/4 toxicity (according to the Common Toxicity Criteria of the National Cancer Institute) was neutropenia in 66% of cycles; however, fever occurred in only 3% of cycles. Daily mitotane was associated with Grade 1/2 nausea, diarrhea, fatigue, and neuropsychiatric changes in 31 of 36 patients (86%).CONCLUSIONSUsing a combination regimen of daily mitotane with infusional doxorubicin, vincristine, and etoposide in patients with metastatic ACC, responses were observed in 22% of patients. The superiority of this combination over single‐agent mitotane is uncertain. The side effects of mitotane made treatment difficult. More effective Pgp antagonists are needed. Cancer 2002;94:2333–43. © 2002 American Cancer Society.DOI 10.1002/cncr.10487

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Adrenal cortical carcinoma a study of 77 cases

Cited by 172 publications

References 10 publications

Unusual tumors associated with the hereditary nonpolyposis colorectal cancer syndrome

Unusual tumors associated with the hereditary nonpolyposis colorectal cancer syndrome

Biosynthesis and metabolism of steroid hormones by human adrenal carcinomas

A phase II trial of combination chemotherapy and surgical resection for the treatment of metastatic adrenocortical carcinoma

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