Diagnosis and Management of Hereditary Adrenal Cancer

Angelousi, Anna; Zilbermint, Mihail; Berthon, Annabel; Espiard, Stéphanie; Stratakis, Constantine A.

doi:10.1007/978-3-319-29998-3_8

Cited by 6 publications

(3 citation statements)

References 68 publications

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“…Li-Fraumeni syndrome (LFS) is a rare autosomal dominant disease associated with changes in the tumor suppressor gene, TP53, located on chromosome 17p. Approximately 50% of LFS patients are known to develop at least one LFS-associated cancer (breast cancer, sarcoma, brain tumor, or ACC) by the age of 30 yr, and 90% develop malignant disease by the age of 60 yr ( 20 ). According to the Chompret’s criteria of LFS ( 21 ), our patient is ‘a proband with ACC at any age of onset, regardless of the family history’, indicating presence of LFS.…”

Section: Discussionmentioning

confidence: 99%

Adrenocortical carcinoma characterized by gynecomastia: A case report

Takeuchi

Yoto

Ishii

et al. 2018

Clin Pediatr Endocrinol

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Abstract.We present a 4-yr-old boy with adrenocortical carcinoma (ACC), diagnosed due to the appearance of gynecomastia as the presenting symptom. Six months prior to admission, an acute growth spurt along with the development of bilateral breast swelling was observed. He did not present any features of virilization, including enlargement of the testes, increase in testis volume, and penis size. Laboratory investigations showed gonadotropin-independent hypergonadism, with low LH/ FSH levels and elevated estradiol/testosterone levels. Abdominal computed tomography revealed a large heterogeneous mass adjacent to the right kidney and below the liver. Pathological investigations of the biopsy specimen demonstrated that the tumor was an ACC. Pre- and post-operative combination chemotherapy with mitotane was administered and surgical resection was carried out. Post-surgery, the elevated estradiol/testosterone concentrations reverted to within the reference range. Urinary steroid profile and tissue concentration analysis of estradiol and testosterone indicated the presence of estrogen in the ACC tissue. An investigation for TP53 gene aberrations revealed the presence of a germline point mutation in exon 4 (c.215C>G (p.Pro72Arg)). In ACC, the most common symptom is virilization, and feminization, characterized by gynecomastia, is very rare. However, a diagnostic possibility of ACC should be considered when we encounter patients who have developed gynecomastia without the influence of causative factors such as obesity or puberty, and do not present with the typical signs of virilization.

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Section: Discussionmentioning

confidence: 99%

Adrenocortical carcinoma characterized by gynecomastia: A case report

Takeuchi

Yoto

Ishii

et al. 2018

Clin Pediatr Endocrinol

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“…Aberrant PRKAR1A expression has been linked to increased tumorigenesis and metastasis in multiple endocrine neoplasia10122526. Additionally, in mesenchymal cells, PRKAR1A deletion also led to tumorigenesis in bone tissues2728.…”

Section: Discussionmentioning

confidence: 99%

PRKAR1A is a functional tumor suppressor inhibiting ERK/Snail/E-cadherin pathway in lung adenocarcinoma

Wang

Cheng

Zheng

et al. 2016

Sci Rep

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Protein Kinase cAMP-Dependent Regulatory Type I Alpha (PRKAR1A) is a tissue-specific extinguisher that transduces a signal through phosphorylation of different target proteins. Loss of PRKAR1A was frequently observed in endocrine neoplasia and stromal cell tumors. However, a few cases were seen in epithelial tumors. Previously, we first found that PRKAR1A was downregulated in lung adenocarcinoma patients. Thus, the present study aimed to clarify its clinical implication and biological function as a tumor suppressor in lung adenocarcinoma. The low levels of PRKAR1A transcript were correlated with tumor progression and poor overall survival. The re-expression of PRKAR1A in H1299 cells suppressed the tumor cell proliferation and migration; stable knockdown (KD) of PRKAR1A in A549 cells enhanced this function both in vitro and in vivo. Moreover, KD of PRKAR1A in A549 cells promoted the statistical colonization of circulating tumor cells to the lungs in nude mice. These effects by PRKAR1A were attributed to inhibiting E-cadherin expression. Elevated E-cadherin significantly suppressed the PRKAR1A-KD induced cell proliferation and migration. Most notably, deletion of PRKAR1A inhibited E-cadherin by activating ERK/Snail signaling. In conclusion, PRKAR1A was a potent suppressor, and through the inhibition of PRKAR1A-ERK-Snail-E-cadherin axis could serve as a potential therapeutic target.

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“…Although most ACCs develop sporadically, a minority of cases are seen in the context of familial cancer syndromes, including Li-Fraumeni syndrome, Beckwith-Wiedemann syndrome, Carney complex, and multiple endocrine neoplasia type 1 ( Angelousi et al 2016 ). As ACC can be the initial presentation of these familial syndromes, it is important to consider further genetic workup.…”

Section: Prognostic Factors In Localized Accmentioning

confidence: 99%

Adjuvant therapy in adrenocortical carcinoma: prognostic factors and treatment options

2022

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Adrenocortical carcinoma (ACC) is a rare cancer with high recurrence rates and heterogeneous clinical behavior. The role of adjuvant therapy remains unclear because of the challenges in collecting high-quality data for a rare cancer. The current treatment recommendations and guidelines for adjuvant therapy are mostly derived retrospectively from national databases and the treatment outcomes of patients seen in referral centers. To better select patients for adjuvant therapy, multiple factors need to be considered including staging, markers of cellular proliferation (such as Ki67%), resection margins, hormonal function, and possibly genetic alterations of the tumor as well as patient-related factors such as age and performance status. Adjuvant mitotane remains the most commonly used adjuvant therapy in ACC based on clinical practice guidelines, though emerging data from ADIUVO trial (mitotane vs. observation in low-risk ACC) suggest that mitotane use in low-risk patients may not be needed. An ongoing clinical trial (ADIUVO-2) is evaluating the role of mitotane vs. mitotane combined with chemotherapy in high-risk ACC. The use of adjuvant therapy has been controversial but can be justified in select patients with positive resection margins or after the resection of localized recurrence. A prospective study is needed to study the role of adjuvant radiation in ACC as radiation is expected to help only with local control without impact on distant microscopic metastases. There are no recommendations or published data about using adjuvant immunotherapy in ACC, but this may be a future study after establishing the efficacy and safety profile of immunotherapy in metastatic ACC.

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Diagnosis and Management of Hereditary Adrenal Cancer

Cited by 6 publications

References 68 publications

Adrenocortical carcinoma characterized by gynecomastia: A case report

Adrenocortical carcinoma characterized by gynecomastia: A case report

PRKAR1A is a functional tumor suppressor inhibiting ERK/Snail/E-cadherin pathway in lung adenocarcinoma

Adjuvant therapy in adrenocortical carcinoma: prognostic factors and treatment options

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