Age-dependent differences in tumor cell polarity in endometrial carcinomas

Saegusa, Makoto; Machida, Daisuke; Okayasu, Isao

doi:10.1007/s00432-002-0327-4

Cited by 5 publications

(4 citation statements)

References 14 publications

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“…In Asian populations, a study conducted in Taiwan revealed a higher incidence of endometrioid carcinoma and lower rates of DMI and LVSI in patients under 50 years old [ 16 ]. The distinct clinical characteristics of younger patients could indicate the biological and genetic diversity of endometrial cancer across various age groups [ 5 , 17 ]. Overall, the previous results showed consistency in certain features, including less DMI and lower grades.…”

Section: Discussionmentioning

confidence: 99%

Clinical characteristics and radiation therapy modality of younger patients with early-stage endometrial cancer, a multicenter study in China’s real world

Zhang,

Wang,

Liu

et al. 2024

BMC Cancer

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Background Endometrial cancer is a prevalent gynecologic malignancy found in postmenopausal women. However, in the last two decades, the incidence of early-stage has doubled in women under 40 years old. This study aimed to investigate the clinical and pathological characteristics and adjuvant therapeutic modalities of both young and not -young patients with early-stage endometrial cancer in China’s real world. Methods This retrospective study analyzed patients with early-stage endometrial cancer at 13 medical institutions in China from 1999 to 2015. The patients were divided into two groups: young (≤ 45 years old) and non-young (> 45 years old). Statistical comparisons were conducted between the two groups for clinical characteristics, pathological features, and survival. The study also identified factors that affect local recurrence-free survival (LRFS) using Cox proportional risk regression analysis. Propensity score matching (1:1) was used to compare the effects of local control between vaginal brachytherapy (VBT) alone and pelvic external beam radiotherapy (EBRT) ± VBT. Results The study involved 1,280 patients, 150 of whom were 45 years old or younger. The young group exhibited a significantly higher proportion of stage II, low-risk, lower uterine segment infiltration (LUSI), and cervical invasion compared to the non-young group. Additionally, the young patients had significantly larger maximum tumor diameters. The young group also had a significantly higher five-year overall survival (OS) and a five-year LRFS. Age is an independent risk factor for LRFS. There was no significant difference in LRFS between young patients with intermediate- to high-risk early-stage endometrial cancer who received EBRT ± VBT and those who received VBT alone. Conclusions In the present study, young patients had better characteristics than the non-young group, while they exhibited higher levels of aggressiveness in certain aspects. The LRFS and OS outcomes were better in young patients. Age is an independent risk factor for LRFS. Additionally, VBT alone may be a suitable option for patients under 45 years of age with intermediate- to high-risk early-stage endometrial cancer, as it reduces the risk of toxic reactions and future second cancers while maintaining similar local control as EBRT.

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Section: Discussionmentioning

confidence: 99%

Clinical characteristics and radiation therapy modality of younger patients with early-stage endometrial cancer, a multicenter study in China’s real world

Zhang,

Wang,

Liu

et al. 2024

BMC Cancer

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“…Our previous study also indicated high p27 expression in endometrial carcinomas adjacent to secretory non-neoplastic endometrium as compared to those surrounded by atrophic or proliferative tissues. 40) Considering that GSK-3β activity is altered by progesterone, 33) it is thus possible that stabilization of β-catenin and p27 in response to progesterone may occur in parallel through different mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Up‐regulation and nuclear localization of β‐catenin in endometrial carcinoma in response to progesterone therapy

Saegusa¹,

Hamano

Kuwata³

et al. 2003

Cancer Science

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Ovarian hormones are considered to be capable of regulating expression of β β β β-catenins. A possible role of β β β β-catenin in alteration of cell morphology has been proposed, but little is known about β β β β-catenin expression during changes in the tumor morphology of endometrial carcinomas induced by progesterone therapy. To clarify changes in expression of β β β β-catenin and their relation to morphological alteration, expression of hormone receptors and several cell kinetic markers, sequential biopsy and hysterectomy specimens of 23 endometrial carcinoma and 6 complex hyperplasia with atypia (atypical hyperplasia) cases receiving progesterone therapy were investigated. In vitro assay was also conducted using two endometrial carcinoma cell lines (HEC265 and Ishikawa) expressing progesterone receptors (PRs). An increase of nuclear β β β β-catenin accumulation was evident during progesterone therapy in endometrial carcinomas and atypical hyperplasias. he most successful approach to the treatment of endometrial carcinoma is hysterectomy with bilateral salpingooophorectomy, combined with cytotoxic chemotherapy and radiation therapy employed for advanced or recurrent tumors. Hormone therapy on the basis of the profound maturation-stimulating effects of progesterone is also applied for tumors in young patients to avoid the necessity of hysterectomy. 1) Such therapy alone, however, is not considered to be sufficient to eradicate carcinomas from the endometrium, since alterations in tumor morphology through cell maturation or differentiation are induced, but not cell death. 2, 3)β-Catenin was originally identified as a major component of the cadherin adhesion system, binding to both E-cadherin cytoplasmic and α-catenin amino-terminal domains.4) The cytoplasmic level of β-catenin is tightly regulated through degradation via the ubiquitin-proteasome pathway, whereby serine and threonine residues in exon 3 are phosphorylated by glycogen synthetase kinase (GSK)-3β and ubiquitinylated by binding to proteins such as adenomatous polyposis coli (APC), and axin. 5)Stabilization of cytoplasmic β-catenin due to up-regulation of wingless/wnt signalling or abnormalities of either APC or β-catenin proteins can lead to its interaction with nuclear transcription factors of the T cell factor-lymphoid enhancer factor (TCF/LEF) family, resulting in activation of target genes. [6][7][8] Recently, ovarian hormones have been reported to be capable of regulating several cell adhesion-related molecules, including E-cadherin, α-and β-catenins and cad-11.9-11) Moreover, changes in expression level and subcellular distribution of the β-catenin occur during morphological alterations through cell differentiation in several colorectal carcinoma cell lines. 12,13) Our previous findings indicated that β-catenin abnormalities may play an important role in relatively early events during the endometrial hyperplasia-carcinoma sequence.14) In the present study, to clarify possible associations between β-catenin and alteration of morphology in respon...

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“…22,38 Thus, distinguishing normal glandular endometrium from well-differentiated adenocarcinoma using 3D culture might not be possible by assessing only gross morphological criteria. Interestingly, endometrial tumors show age-dependent differences in polarity based on parameters such as the position of the cell nucleus and the formation of glandular convolution, 39 with abundance of nonpolarized neoplasms in older patients. This observation suggests that apical polarity might be an important feature to scrutinize for the classification of endometrial neoplasia.…”

Section: D Cultures To Develop Diagnostic Tools For Neoplasiamentioning

confidence: 99%

Three-Dimensional Cell Culture to Model Epithelia in the Female Reproductive System

2007

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In vitro 3-dimensional (3D) cell cultures produce valuable models that mimic 3D tissue organization and function and enhance the understanding of cell/tissue function under normal and pathological situations. Tissue function depends on the interactions between cells and the extracellular matrix; thus, effective 3D cell cultures rely on the use of appropriate extracellular matrix cues. Noticeable progress in 3D cell culture was obtained from studies with epithelial cells from organs of the female reproductive system including the mammary glands, the uterus, and the ovaries. These models show that replicating normal tissue organization in the resting phase is a prerequisite for appropriate physiological and pathological investigations. The authors' goals are to explain the importance of mimicking detailed aspects of normal epithelial organization and function, such as basoapical polarity, in 3D cell culture and to discuss how effective 3D cell culture models can lead to meaningful applications in reproductive biology.

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Age-dependent differences in tumor cell polarity in endometrial carcinomas

Abstract: These findings indicate that in endometrial carcinomas, the age-dependent differences in tumor cell polarity may be related to status of endogenous ovarian hormones, closely linked with cell proliferation and some prognostic factors.

Cited by 5 publications

References 14 publications

Clinical characteristics and radiation therapy modality of younger patients with early-stage endometrial cancer, a multicenter study in China’s real world

Clinical characteristics and radiation therapy modality of younger patients with early-stage endometrial cancer, a multicenter study in China’s real world

Up‐regulation and nuclear localization of β‐catenin in endometrial carcinoma in response to progesterone therapy

Three-Dimensional Cell Culture to Model Epithelia in the Female Reproductive System

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