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Fulltext Role of co-expression of estrogen receptor beta and Ki67 in prostate adenocarcinoma

Azizan N, Hayati F, Tizen NMS, Farouk WI, Masir N

Investig Clin Urol, 2018 07;59(4):232-237.
PMID: 29984337 DOI: 10.4111/icu.2018.59.4.232

Purpose: To evaluate the expression of estrogen receptor (ER)-beta and Ki67 in prostate cancer and study their relationship.
Materials and Methods: We analyzed 101 cases of prostate adenocarcinoma diagnosed from January 2011 to June 2015 in 100 patients. Immunohistochemical staining of ER-beta and Ki67 was analyzed according to Gleason score categorized into prognostic groups of 1 to 5. Double-immunofluorescent staining of ER-beta and Ki67 was performed in a total of 20 cases to study the co-expression and the relationship between these markers within the same tumor.
Results: A total of 53 of 101 cases (52.5%) were positive for ER-beta expression. There was a positive correlation whereby a high percentage of ER-beta expression was seen in the higher prognostic groups (groups 4 and 5; p=0.007). High Ki67 expression was observed in the higher prognostic group, whereas low Ki67 or negative expression was found in the lower prognostic group (p<0.001). The majority of cases evaluated with double-immunofluorescent staining (14/20) showed co-expression of ER-beta and Ki67 at the individual cell level.
Conclusions: ER-beta and Ki67 are independent tumor markers in high prognostic groups. Hence, co-expression of ER-beta and Ki67 indicates a more aggressive tumor with a poorer prognosis.

Matched MeSH terms: Estrogen Receptor beta/metabolism*
The expression of sex steroid receptors and sex steroid-synthesizing/metabolizing enzymes in metastasized lymph nodes of prostate cancer

Nakamura Y, Ise K, McNamara KM, Azmahani A, Sato S, Fujishima F, et al.

Hum Pathol, 2019 02;84:124-132.
PMID: 30290162 DOI: 10.1016/j.humpath.2018.09.011

The expression statuses of sex steroid receptors and sex steroid-synthesizing/metabolizing enzymes have been reported in primary prostate cancer lesions, but that in metastatic lymph nodes has remained unknown. Therefore, in this study, we immunolocalized these proteins in primary tumors and paired metastatic lymph nodes of prostate cancer and correlated the findings with clinicopathological factors of individual patients. The expression statuses of AR and ER β was significantly increased in metastatic lymph nodes compared with primary lesions, whereas that of 17βHSD1, 17βHSD2, 17βHSD5, and STS immunoreactivity was decreased in metastatic lymph nodes. In metastatic lymph nodes, the status of 5α2 was significantly correlated with that of AR. In addition, 17βHSD5-, 5α1-, STS-, and EST-positive cases were significantly associated with Gleason score (GS) status (GS > 8 versus GS < 7) in metastatic lymph nodes. Results of our present study did demonstrate that in situ androgen and estrogen metabolism and action play roles in pathophysiology of prostate cancer in metastatic lymph nodes, but these steroidogenic effects could be different from those in primary lesions.

Matched MeSH terms: Estrogen Receptor beta/metabolism
Immunohistochemical detection of phospho-Akt, phospho-BAD, HER2 and oestrogen receptors alpha and beta in Malaysian breast cancer patients

Seow HF, Yip WK, Loh HW, Ithnin H, Por P, Rohaizak M

Pathol Oncol Res, 2010 Jun;16(2):239-48.
PMID: 19882362 DOI: 10.1007/s12253-009-9216-3

Activation of Akt signaling pathway has been documented in various human malignancies, including breast carcinoma. The objective of this study is to determine the incidence of Akt phosphorylation in breast tumours and its relationship with expression of ER-alpha, ER-beta, HER2, Ki-67 and phosphorylated Bcl-2 associated death domain (p-BAD). Immunohistochemical staining was performed to detect these molecules on 43 paraffin-embedded breast tumour tissues with commercially available antibodies. Eighteen (41.9%), 3 (7.0%), 23 (53.5%), 35 (81.4%), 21 (48.8%), 29 (67.4%), and 34 (81.0%) of breast tumours were positive for nuclear ER-alpha, nuclear ER-beta, membranous HER2, cytonuclear p-Akt (Thr308), p-Akt (Ser473), p-BAD and Ki-67, respectively. ER-alpha expression was inversely correlated with HER2 and Ki-67 (P = 0.041 and P = 0.040, respectively). The p-Akt (Ser473) was correlated with increased level of p-BAD (Ser136) (P = 0.012). No relationship of Akt phosphorylation with HER2, ER-alpha or ER-beta was found. The p-Akt (Ser473) immunoreactivity was significantly higher in stage IV than in stage I or II (P = 0.036 or P = 0.009). The higher Ki-67 and lower ER-alpha expression showed an association with patient age of <50 years (P = 0.004) and with positive nodal status (P = 0.033), respectively. Our data suggest that the Akt phosphorylation and inactivation of its downstream target, BAD may play a role in survival of breast cancer cell. This study does not support the simple model of linear HER2/PI3K/Akt pathway in breast cancer.

Matched MeSH terms: Estrogen Receptor beta/metabolism*
Sexual maturation modulates expression of nuclear receptor types in laser-captured single cells of the cichlid (Oreochromis niloticus) pituitary

Kitahashi T, Ogawa S, Soga T, Sakuma Y, Parhar I

Endocrinology, 2007 Dec;148(12):5822-30.
PMID: 17823257

The role of steroid/thyroid hormones in the regulation of endocrine cells at the level of the pituitary has remained unclear. Therefore, using single-cell quantitative real-time PCR, we examined absolute amounts of transcripts for nuclear receptors [estrogen receptors (ERs) alpha, beta, and gamma; androgen receptors (ARs) a and b; glucocorticoid receptors (GRs) 1, 2a, and 2b; and thyroid hormone receptors (TRs) alpha1, alpha2, and beta] in pituitary cells of immature (IM) and mature (M) male tilapia, Oreochromis niloticus. In the two reproductive stages, ACTH cells expressed only ERbeta, whereas all other pituitary cell types expressed ERalpha + beta, and a subpopulation coexpressed ARa, ARb, GR1, GR2b, and TRbeta but lacked ERgamma, GR2a, TRalpha1, and TRalpha2. IM males had high percentages of LH cells (IM 46.0% vs. M 10.0%), GH cells (IM 23.3% vs. M 7.9%), and prolactin cells (IM 68.8% vs. M 6.0%) with ERbeta, and TSH cells (IM 19.2% vs. M 0.0%) and MSH cells (IM 25.6% vs. M 0.0%) with ERalpha + TRbeta. A high percentage of FSH cells in IM males expressed ERbeta (IM 46.9% vs. M 18.8%), and FSH cells in M males showed significantly high GR1 transcripts (IM 76.0 +/- 5.0 vs. M 195.0 +/- 10.7 copies per cell; P < 0.05), suggesting that FSH cells are regulated differently in the two reproductive stages. Coexpression of ERalpha + beta in high percentages of cells of the GH family (GH, IM 43.8% vs. M 14.3%; prolactin, IM 8.3% vs. M 59.7%; somatolactin, IM 22.2% vs. M 42.2%) suggests that the expression of both ERs is important for functionality. Thus, differential coexpression of genes for nuclear receptors in subpopulations of pituitary cell types suggests multiple steroid/thyroid hormone regulatory pathways at the level of the pituitary during the two reproductive stages.

Matched MeSH terms: Estrogen Receptor beta/metabolism