Uterine leiomyosarcomas are characterized by high p16, p53 and MIB1 expression in comparison with usual leiomyomas, leiomyoma variants and smooth muscle tumours of uncertain malignant potential

O’Neill, Ciaran; McBride, H A; Connolly, L E; McCluggage, W. Glenn

doi:10.1111/j.1365-2559.2007.02699.x

Cited by 167 publications

(114 citation statements)

References 28 publications

Supporting

Mentioning

100

Contrasting

Unclassified

Order By: Relevance

“…In colorectal cancer, p16 Ink4a exhibits a similar pattern, showing strong nuclear/ cytoplasmic positivity (about 80%) in adenomas and in primary or metastatic adenocarcinomas, whereas negativity or low nuclear expression is observed in normal mucosa and in benign conditions (Dai et al, 2000;Di Vinci et al, 2005;Zhao et al, 2006). In addition, in non-epithelial tumors such as astrocytomas or uterine leiomyosarcomas, p16 Ink4a overexpression can be detected in both the nucleus and the cytoplasm, and this compartmentalized staining has been associated with high-grade malignant phenotypes (Beasley et al, 2003;Arifin et al, 2006;O'Neill et al, 2007). Further supporting this hypothesis, Haller et al (2010) have recently described the association between p16 Ink4a cytoplasmic overexpression and p16 Ink4a nuclear downregulation, with poor prognosis in gastrointestinal stromal tumor.…”

Section: Subcellular Location Of P16 Ink4a Overexpressionmentioning

confidence: 94%

“…However, p16 Ink4a can also be overexpressed in tumors, and few studies have been performed to elucidate this fact, except in the case of human papilloma virus (HPV)-related neoplasms (Milde-Langosch et al, 2001;Garcia et al, 2004;Arifin et al, 2006;Ivanova et al, 2007;O'Neill et al, 2007;Lam et al, 2008). In fact, p16 Ink4a overexpression in some types of tumors, such as cervical cancer, head and neck cancer and perianal lesions is used as a diagnostic tool and has been directly associated with infection by high-risk genotypes of HPV (Mulvany et al, 2008).…”

Section: P16 Ink4a Overexpression In Tumorsmentioning

confidence: 99%

See 1 more Smart Citation

p16Ink4a overexpression in cancer: a tumor suppressor gene associated with senescence and high-grade tumors

et al. 2011

View full text Add to dashboard Cite

p16 Ink4a is a protein involved in regulation of the cell cycle. Currently, p16 Ink4a is considered a tumor suppressor protein because of its physiological role and downregulated expression in a large number of tumors. Intriguingly, overexpression of p16 Ink4a has also been described in several tumors. This review attempts to elucidate when and why p16 Ink4a overexpression occurs, and to suggest possible implications of p16 Ink4a in the diagnosis, prognosis and treatment of cancer.

show abstract

Section: Subcellular Location Of P16 Ink4a Overexpressionmentioning

confidence: 94%

Section: P16 Ink4a Overexpression In Tumorsmentioning

confidence: 99%

p16Ink4a overexpression in cancer: a tumor suppressor gene associated with senescence and high-grade tumors

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Ki67 also shows a remarkable degree of overlap between leiomyoma with bizarre nuclei and leiomyosarcoma, and thus, it is not helpful in most instances. 34,[37][38][39] Yet, other cell cycle regulatory markers including p21 and p27 appear to show extensive overlap between these two categories of smooth muscle tumors. 31 MED12 mutations that are common in typical leiomyomas [40][41][42][43] are uncommon in leiomyomas with bizarre nuclei but also rare in leiomyosarcomas.…”

Section: Tumor Cell Necrosismentioning

confidence: 99%

Practical issues in uterine pathology from banal to bewildering: the remarkable spectrum of smooth muscle neoplasia

Oliva

2016

Modern Pathology

View full text Add to dashboard Cite

Among mesenchymal tumors of the uterus, smooth muscle neoplasms are most common. The wide morphologic spectrum, especially within the category of leiomyomas, is responsible for diagnostic problems more frequently with leiomyosarcoma (including mitotically active, apoplectic, and leiomyoma with bizarre nuclei) but also with endometrial stromal tumors. In the former scenario, clinical information, gross appearance as well as strict utilization of morphologic criteria including cytologic atypia, mitotic activity, and tumor cell necrosis are clues in establishing the correct diagnosis. It is important to keep in mind that mitotic rate thresholds vary for the different subtypes of leiomyosarcoma. Of note, p16 should be used with caution in supporting a diagnosis of leiomyosarcoma as it is often positive in leiomyomas with bizarre nuclei and leiomyomas with apoplectic change (in the latter most frequently and more intense near areas of necrosis). MED12 mutations have also a very limited role in this differential diagnosis. Endometrial stromal tumors are by far, less common than smooth muscle tumors, but can be confused with leiomyosarcomas if they are associated with an undifferentiated uterine sarcoma and the low-grade component is overlooked or they have a myxoid/fibroblastic morphology. The differential diagnosis may be confounded if the latter is associated with a high-grade endometrial stromal sarcoma. It is important to highlight that CD10 is not a reliable marker in these differentials and should be used as a part of a panel of antibodies that also includes desmin and h-caldesmon. Two other recently categorized tumors in the uterus that merit special mention are PEComa and inflammatory myofibroblastic tumor as they enter in the differential diagnosis of smooth muscle tumors. PEComa may be part of the tuberous sclerosis syndrome and may show either a predominantly epithelioid or spindle morphology or combination thereof. Rarely, it may contain melanin pigment. There is variable positivity for HMB-45, MelanA, MiTF, and CathepsinK, and some tumors have been shown to express TFE-3 especially when associated with "clear cell" morphology. Patients with adverse outcome have tumors with ≥ 2 of the following features: ≥ 5 cm, infiltration, high-grade cytologic features, mitotic rate ≥ 1/50 high-power fields, necrosis, or lymphovascular invasion. Inflammatory myofibroblastic tumor is important to recognize as it often mimics myxoid smooth muscle tumors, either benign or malignant. The presence of an associated lymphoplasmacytic infiltrate should alert to that possibility and ALK studies (immunostain or FISH) are helpful in establishing this diagnosis. These tumors can behave in a malignant manner if large, associated with abundant myxoid change, brisk mitotic rate or show tumor cell necrosis.

show abstract

“…3 To complement the morphological analysis in difficult cases, a variety of ancillary laboratory techniques (p53, p16, bcl2, and ki67) have been implemented but without any significant improvement in the diagnosis. [4][5][6][7][8][9] By trying to avoid the diagnosis of STUMP, the pathologist could risk under-or over diagnosing a difficult lesion with the inherent risk of under or overtreatment, which could have dramatic consequences for the patient, especially in her reproductive age (hysterectomy precluding fertility).…”

mentioning

confidence: 99%

Uterine smooth muscle tumor analysis by comparative genomic hybridization: a useful diagnostic tool in challenging lesions

et al. 2015

View full text Add to dashboard Cite

The diagnosis and management of uterine smooth muscle tumors with uncertain malignant potential (STUMP) is often challenging, and genomic data on these lesions as well as on uterine smooth muscle lesions are limited. We tested the hypothesis that genomic profile determination by array-CGH could split STUMP into a benign group with scarce chromosomal alterations akin to leiomyoma and a malignant group with high chromosomal instability akin to leiomyosarcoma. Array-CGH genomic profile analysis was conducted for a series of 29 cases of uterine STUMP. A group of ten uterine leiomyomas and ten uterine leiomyosarcomas served as controls. The mean age was 50 years (range, 24-85) and the follow-up ranged from 12 to 156 months (average 70 months). Since STUMP is a heterogenous group of tumors with genomic profiles that can harbor few to many chromosomal alterations, we compared genomic indices in leiomyomas and leiomyosarcomas and set a genomic index ¼ 10 threshold. Tumors with a genomic index o10 were classified as nonrecurring STUMPs and those with a genomic index 410 represented STUMPs with recurrences and unfavorable outcomes. Hence, the genomic index threshold splits the STUMP category into two groups of tumors with different outcomes: a group comparable to leiomyomas and another similar to leiomyosarcomas, but more indolent. In our STUMP series, genomic analysis by array-CGH is an innovative diagnostic tool for problematic smooth muscle uterine lesions, complementary to the morphological evaluation approach. We provide an improved classification method for distinguishing truly malignant tumors from benign lesions within the category of STUMP, especially those with equivocal morphological features.

show abstract

Uterine leiomyosarcomas are characterized by high p16, p53 and MIB1 expression in comparison with usual leiomyomas, leiomyoma variants and smooth muscle tumours of uncertain malignant potential

Cited by 167 publications

References 28 publications

p16Ink4a overexpression in cancer: a tumor suppressor gene associated with senescence and high-grade tumors

p16Ink4a overexpression in cancer: a tumor suppressor gene associated with senescence and high-grade tumors

Practical issues in uterine pathology from banal to bewildering: the remarkable spectrum of smooth muscle neoplasia

Uterine smooth muscle tumor analysis by comparative genomic hybridization: a useful diagnostic tool in challenging lesions

Contact Info

Product

Resources

About