Immunohistochemical analysis of oestrogen receptors, progesterone receptors and Ki-67 in leiomyoma and myometrium during the menstrual cycle and pregnancy

Kawaguchi, Keizaburo; Fujii, Shingo; Konishi, Ikuo; Iwai, Toshiko; Nanbu, Yoshihiko; Nonogaki, Hirofumi; Ishikawa, Yuichi; Mori, Takahide

doi:10.1007/bf01606522

Cited by 98 publications

(62 citation statements)

References 15 publications

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“…This study has demonstrated wide expression of ER alpha and PR in nearly 100% of uterine LMA and low level of AR expression in the uterine tissues which were in accordance to previous studies (Kawaguchi, 1991;Leitao, 2004). Although the level of sex steroid receptors were similar in adjacent myometriums and uterine leiomyomas of all cases, AhR was strongly stained and significantly overexpressed (p=0.034, OR=1.667) in uterine LMA.…”

Section: Discussionsupporting

confidence: 91%

Role of Endocrine Disrupting Chemicals in the Occurrence of Benign Uterine Leiomyomata: Special Emphasis on AhR Tissue Levels

Bidgoli¹,

Khorasani²,

Keihan³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Section: Discussionsupporting

confidence: 91%

Role of Endocrine Disrupting Chemicals in the Occurrence of Benign Uterine Leiomyomata: Special Emphasis on AhR Tissue Levels

Bidgoli¹,

Khorasani²,

Keihan³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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“…These tumors do not only morphologically resemble uterine leiomyomas, but they also are positive for ER, which is similar to uterine leiomyomas (21,22) and dissimilar to GISTs, which are ER-negative according to our results. Therefore, ER immunostaining is a valuable aid to separate the uterine type leiomyomas from GISTs.…”

Section: Discussionsupporting

confidence: 70%

Immunohistochemical Spectrum of GISTs at Different Sites and Their Differential Diagnosis with a Reference to CD117 (KIT)

2000

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Gastrointestinal (GI) stromal tumor (GIST) is the designation for the major subset of GI mesenchymal tumors and encompasses most tumors previously classified as GI smooth muscle tumors. Although GISTs typically express CD117 (KIT), often express CD34, and sometimes express ␣-smooth muscle actin (SMA), the relative frequency of these markers has not been characterized in large series of GISTs of different sites, and the CD117 expression has not been fully characterized in intra-abdominal tumors. In this study, we immunohistochemically analyzed 292 GISTs throughout the GI tract, including omentum and mesentery, and compared the immunoreactivities with 211 other tumors that may enter in the differential diagnosis. GISTs were defined in this study as CD117-positive primary spindled or epithelioid mesenchymal tumors of the GI tract, omentum, or mesentery. The CD34 positivity of GISTs varied from 47% in small bowel to 96 to 100% in rectum and esophagus, whereas SMA expression showed the opposite patterns and was most frequent in the GISTs of small bowel (47%) and rarest in the GISTs of rectum and esophagus (10 -13%). Desmin was seen only occasionally. S100 positivity was rare but was seen most frequently in small intestinal GISTs (15%). True leiomyomas from esophagus, muscularis mucosae of colorectum, and pericolic leiomyomas similar to uterine leiomyomas were negative for CD117 and CD34 and positive for SMA and desmin (46 of 46). Inflammatory fibroid polyps of stomach and small intestine were negative for CD117 but were often positive for CD34 (6 of 8) and variable for SMA (3 of 8). Inflammatory myofibroblastic tumors involving gastric or colonic wall were negative for CD117 but some showed CD117-positive endothelia. GI schwannomas were all negative for CD117 and positive for S100 protein (11 of 11). Extremely focal CD117 positivity was seen in the neoplastic cells of some retroperitoneal leiomyosarcomas and liposarcomas. Among other CD117-positive tumors were intestinal metastatic melanomas (8 of 11) and extraskeletal Ewing's sarcomas (5 of 11), two of which were abdominal. In conclusion, strong CD117 expression defines most primary GI mesenchymal tumors as GISTs, which show different patterns for CD34 and SMA in various parts of the GI tract. Some unrelated CD117-positive tumors (melanomas, Ewing's sarcomas) should not be confused with GISTs.

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“…Average numbers of Ki-67 positive cells per cross-section in 3-to 5-mo-old WT and the transgenic mice were 1.42 ± 0.99 and 6.17 ± 2.29, respectively. Extent of mitotic activity present in the transgenic myometrium was comparable to the reported level of mitotic cells in uterine leiomyomas (31).…”

Section: Transgenic Overexpression Of Hgpr10 In Mouse Myometrium Leadsupporting

confidence: 77%

Loss of the repressor REST in uterine fibroids promotes aberrant G protein-coupled receptor 10 expression and activates mammalian target of rapamycin pathway

Varghese¹,

Koohestani²,

McWilliams³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Uterine fibroids (leiomyomas) are the most common tumors of the female reproductive tract, occurring in up to 77% of reproductiveaged women, yet molecular pathogenesis remains poorly understood. A role for atypically activated mammalian target of rapamycin (mTOR) pathway in the pathogenesis of uterine fibroids has been suggested in several studies. We identified that G protein-coupled receptor 10 [GPR10, a putative signaling protein upstream of the phosphoinositide 3-kinase-protein kinase B/AKT-mammalian target of rapamycin (PI3K/AKT-mTOR) pathway] is aberrantly expressed in uterine fibroids. The activation of GPR10 by its cognate ligand, prolactin releasing peptide, promotes PI3K-AKT-mTOR pathways and cell proliferation specifically in cultured primary leiomyoma cells. Additionally, we report that RE1 suppressing transcription factor/neuron-restrictive silencing factor (REST/NRSF), a known tumor suppressor, transcriptionally represses GPR10 in the normal myometrium, and that the loss of REST in fibroids permits GPR10 expression. Importantly, mice overexpressing human GPR10 in the myometrium develop myometrial hyperplasia with excessive extracellular matrix deposition, a hallmark of uterine fibroids. We demonstrate previously unrecognized roles for GPR10 and its upstream regulator REST in the pathogenesis of uterine fibroids. Importantly, we report a unique genetically modified mouse model for a gene that is misexpressed in uterine fibroids.

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Immunohistochemical analysis of oestrogen receptors, progesterone receptors and Ki-67 in leiomyoma and myometrium during the menstrual cycle and pregnancy

Cited by 98 publications

References 15 publications

Role of Endocrine Disrupting Chemicals in the Occurrence of Benign Uterine Leiomyomata: Special Emphasis on AhR Tissue Levels

Role of Endocrine Disrupting Chemicals in the Occurrence of Benign Uterine Leiomyomata: Special Emphasis on AhR Tissue Levels

Immunohistochemical Spectrum of GISTs at Different Sites and Their Differential Diagnosis with a Reference to CD117 (KIT)

Loss of the repressor REST in uterine fibroids promotes aberrant G protein-coupled receptor 10 expression and activates mammalian target of rapamycin pathway

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