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Potential biomarker for human uterine leiomyosarcoma.

Hayashi T, Horiuchi A, Aburatani H, Ishiko O, Yaegashi N, Kanai Y, Zharhary D, Shiozawa T, Tonegawa S, Konishi I - J Clin Med Res (2014)

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology and Infectious Disease, Shinshu University School of Medicine, Matsumoto, Nagano 390-8621, Japan ; Promoting Business Using Advanced Technology, Japan Science and Technology Agency (JST), Chiyoda, Tokyo 102-8666, Japan ; SIGMA-Aldrich Collaboration Laboratory.

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Sarcomas are a rare form of malignant tumor, with less than 15,000 new cases being diagnosed each year in the United States... Uterine mesenchymal tumors that develop in the myometrium have traditionally been divided into benign uterine usual LMA, cellular LMA and malignant Ut-LMS based on cytological atypia, mitotic activity and other criteria... The non-standard subtypes of uterine mesenchymal tumors such as the epithelioid and myxoid types are classified in a different manner using these features; therefore, a diagnostic method needs to be established that can identify non-standard smooth muscle differentiation... High estrogen levels have been shown to significantly influence the development of tumors in the uterine body... However, a relationship has not yet been reported between the development of Ut-LMS and hormonal conditions, and no obvious risk factors have been identified... The identification of risk factors associated with the development of human Ut-LMS will contribute significantly to the development of preventive and therapeutic treatments... Pathological examinations revealed that the ability to induce the expression of LMP2/β1i and calponin h1 was markedly lower in human Ut-LMS tissues than in uterine LMA or a normal myometrium located in the same section, and the expression of cyclin E was markedly high in human Ut-LMS tissues only... The histological findings of skeletal muscle and rectum lesions were consistent with metastatic Ut-LMS... Western blotting and RT-PCR experiments revealed that LMP2/β1i was expressed in a normal myometrium, but not in human Ut-LMS, and both findings strongly supported the pathological results... Although we previously demonstrated that the abnormal expression of the ovarian steroid receptors, Tp53, ki-67 and mutations in Tp53 were frequently associated with Ut-LMS, the defective expression of LMP2/β1i and calponin h1 appeared to be more characteristic of human Ut-LMS than these factors (Fig. 1)... The histopathological characteristics of human uterine mesenchymal tumors including mitotically active leiomyoma, bizarre leiomyoma, lipoleiomyoma, undifferentiated endometrial sarcoma, epithelioid variant leiomyosarcoma, myxoid variant leiomyosarcoma, smooth muscle tumors of uncertain malignant potential (STUMP) and leiomyomatoid angiomatous neuroendocrine tumor (LANT) have already been summarized.

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Summary of IHC experiments for p53, LMP2, cyclin B, calponin h1 and ki-67 expression levels in leiomyoma (LMA) and leiomyosarcoma (LMS). IHC experiments were performed using seven LMA tissue samples and 23 LMS tissue samples obtained from patients with LMA and/or LMS. Data were quantified using WinROOF Ver.6.3.0 software (Mitani Co., Ltd, Fukui, Japan). P vales were generated using a t-test. Data are representative of three experiments. +++: diffuse-positive (homogeneous distribution with more than 90% of cells stained), -: negative (no stained cells).
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Figure 1: Summary of IHC experiments for p53, LMP2, cyclin B, calponin h1 and ki-67 expression levels in leiomyoma (LMA) and leiomyosarcoma (LMS). IHC experiments were performed using seven LMA tissue samples and 23 LMS tissue samples obtained from patients with LMA and/or LMS. Data were quantified using WinROOF Ver.6.3.0 software (Mitani Co., Ltd, Fukui, Japan). P vales were generated using a t-test. Data are representative of three experiments. +++: diffuse-positive (homogeneous distribution with more than 90% of cells stained), -: negative (no stained cells).

Mentions: The non-standard subtypes of uterine mesenchymal tumors such as the epithelioid and myxoid types have been classified in a different manner using these features; therefore, a diagnostic method needs to be established that can identify non-standard smooth muscle differentiation [5, 6]. Pathological studies have been performed to demonstrate the validity and reliability of LMP2/β1i as a diagnostic biomarker when combined with other candidate molecules, such as cyclin E and calponin h1, which reportedly function as anti-oncogenic factors in human Ut-LMS. Pathological examinations revealed that the ability to induce the expression of LMP2/β1i and calponin h1 was markedly lower in human Ut-LMS tissues than in uterine LMA or a normal myometrium located in the same section, and the expression of cyclin E was markedly high in human Ut-LMS tissues only [13-16]. The histological findings of skeletal muscle and rectum lesions were consistent with metastatic Ut-LMS [13, 14]. Western blotting and RT-PCR experiments revealed that LMP2/β1i was expressed in a normal myometrium, but not in human Ut-LMS, and both findings strongly supported the pathological results [13, 14, 16, 17]. Although we previously demonstrated that the abnormal expression of the ovarian steroid receptors, Tp53, ki-67 and mutations in Tp53 were frequently associated with Ut-LMS, the defective expression of LMP2/β1i and calponin h1 appeared to be more characteristic of human Ut-LMS than these factors [14, 15, 18-20] (Fig. 1).


Potential biomarker for human uterine leiomyosarcoma.

Hayashi T, Horiuchi A, Aburatani H, Ishiko O, Yaegashi N, Kanai Y, Zharhary D, Shiozawa T, Tonegawa S, Konishi I - J Clin Med Res (2014)

Summary of IHC experiments for p53, LMP2, cyclin B, calponin h1 and ki-67 expression levels in leiomyoma (LMA) and leiomyosarcoma (LMS). IHC experiments were performed using seven LMA tissue samples and 23 LMS tissue samples obtained from patients with LMA and/or LMS. Data were quantified using WinROOF Ver.6.3.0 software (Mitani Co., Ltd, Fukui, Japan). P vales were generated using a t-test. Data are representative of three experiments. +++: diffuse-positive (homogeneous distribution with more than 90% of cells stained), -: negative (no stained cells).
© Copyright Policy - open access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4125337&req=5

Figure 1: Summary of IHC experiments for p53, LMP2, cyclin B, calponin h1 and ki-67 expression levels in leiomyoma (LMA) and leiomyosarcoma (LMS). IHC experiments were performed using seven LMA tissue samples and 23 LMS tissue samples obtained from patients with LMA and/or LMS. Data were quantified using WinROOF Ver.6.3.0 software (Mitani Co., Ltd, Fukui, Japan). P vales were generated using a t-test. Data are representative of three experiments. +++: diffuse-positive (homogeneous distribution with more than 90% of cells stained), -: negative (no stained cells).
Mentions: The non-standard subtypes of uterine mesenchymal tumors such as the epithelioid and myxoid types have been classified in a different manner using these features; therefore, a diagnostic method needs to be established that can identify non-standard smooth muscle differentiation [5, 6]. Pathological studies have been performed to demonstrate the validity and reliability of LMP2/β1i as a diagnostic biomarker when combined with other candidate molecules, such as cyclin E and calponin h1, which reportedly function as anti-oncogenic factors in human Ut-LMS. Pathological examinations revealed that the ability to induce the expression of LMP2/β1i and calponin h1 was markedly lower in human Ut-LMS tissues than in uterine LMA or a normal myometrium located in the same section, and the expression of cyclin E was markedly high in human Ut-LMS tissues only [13-16]. The histological findings of skeletal muscle and rectum lesions were consistent with metastatic Ut-LMS [13, 14]. Western blotting and RT-PCR experiments revealed that LMP2/β1i was expressed in a normal myometrium, but not in human Ut-LMS, and both findings strongly supported the pathological results [13, 14, 16, 17]. Although we previously demonstrated that the abnormal expression of the ovarian steroid receptors, Tp53, ki-67 and mutations in Tp53 were frequently associated with Ut-LMS, the defective expression of LMP2/β1i and calponin h1 appeared to be more characteristic of human Ut-LMS than these factors [14, 15, 18-20] (Fig. 1).

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology and Infectious Disease, Shinshu University School of Medicine, Matsumoto, Nagano 390-8621, Japan ; Promoting Business Using Advanced Technology, Japan Science and Technology Agency (JST), Chiyoda, Tokyo 102-8666, Japan ; SIGMA-Aldrich Collaboration Laboratory.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

Sarcomas are a rare form of malignant tumor, with less than 15,000 new cases being diagnosed each year in the United States... Uterine mesenchymal tumors that develop in the myometrium have traditionally been divided into benign uterine usual LMA, cellular LMA and malignant Ut-LMS based on cytological atypia, mitotic activity and other criteria... The non-standard subtypes of uterine mesenchymal tumors such as the epithelioid and myxoid types are classified in a different manner using these features; therefore, a diagnostic method needs to be established that can identify non-standard smooth muscle differentiation... High estrogen levels have been shown to significantly influence the development of tumors in the uterine body... However, a relationship has not yet been reported between the development of Ut-LMS and hormonal conditions, and no obvious risk factors have been identified... The identification of risk factors associated with the development of human Ut-LMS will contribute significantly to the development of preventive and therapeutic treatments... Pathological examinations revealed that the ability to induce the expression of LMP2/β1i and calponin h1 was markedly lower in human Ut-LMS tissues than in uterine LMA or a normal myometrium located in the same section, and the expression of cyclin E was markedly high in human Ut-LMS tissues only... The histological findings of skeletal muscle and rectum lesions were consistent with metastatic Ut-LMS... Western blotting and RT-PCR experiments revealed that LMP2/β1i was expressed in a normal myometrium, but not in human Ut-LMS, and both findings strongly supported the pathological results... Although we previously demonstrated that the abnormal expression of the ovarian steroid receptors, Tp53, ki-67 and mutations in Tp53 were frequently associated with Ut-LMS, the defective expression of LMP2/β1i and calponin h1 appeared to be more characteristic of human Ut-LMS than these factors (Fig. 1)... The histopathological characteristics of human uterine mesenchymal tumors including mitotically active leiomyoma, bizarre leiomyoma, lipoleiomyoma, undifferentiated endometrial sarcoma, epithelioid variant leiomyosarcoma, myxoid variant leiomyosarcoma, smooth muscle tumors of uncertain malignant potential (STUMP) and leiomyomatoid angiomatous neuroendocrine tumor (LANT) have already been summarized.

No MeSH data available.


Related in: MedlinePlus