Effect of menopause on hormonal receptors in ampullae of the fallopian tube with a special reference to the p53 signature.

OBJECTIVES: Age-related changes in the expression of hormonal receptors have not been well examined in the fallopian tube (FT). We herein report the effect of menopause on the hormone receptors in ampullae of the FTs (AFTs), in comparison with cortical inclusion cysts (CICs) of the ovary. METHODS: A total of 84 AFTs and 16 fimbriae of FTs, which were obtained from 26 premenopausal and 58 postmenopausal women; and 27 postmenopausal CICs were immunohistochemically studied for the expression of p53, Ki-67, estrogen receptor-alpha (ER-α), and progesterone receptor A (PRA). Apoptotic cells were identified using a TUNEL assay. RESULTS: Postmenopausal AFTs showed a significantly lower labeling index (LI) for Ki-67 (P<0.001), apoptosis (P=0.03), and PRA (P<0.001) than premenopausal AFTs. No significant correlation with immunohistochemical markers was found in premenopausal AFTs, but the LI for PRA was positively correlated with that for Ki-67 (P=0.004) and inversely with that for p53 (P=0.023) in postmenopausal AFTs. The expression of immunohistochemical markers was closely correlated between ampullae and fimbriae of the FT. The p53 signature (p53S) was detected in five postmenopausal AFTs (mean age: 70.2 years) and was not detected in any CICs. The immunohistochemical profile of p53S was low expression of Ki-67, apoptosis, and PRA, and high expression of ER-α. The expression of PRA in CICs was significantly higher than that in AFTs (P=0.001). CONCLUSION: The expression of PRA was significantly lower in postmenopausal AFTs than in premenopausal AFTs, whereas the expression of PRA was well preserved in postmenopausal CICs.

Immunohistochemical Analysis of the Effect of Dienogest on Ovarian Endometriotic Cysts.

Dienogest is a novel progestin with potent oral progestational activity that inhibits the clinical symptoms of endometriosis. We herein evaluated the effect of dienogest on ovarian endometriotic cysts via immunohistochemistry. Ovarian endometriotic cyst specimens were collected from 12 patients treated with dienogest and 20 patients not treated with hormones (controls). The expression of estrogen receptor (ER)-α, progesterone receptor A (PRA), and Ki-67 was studied by immunohistochemistry. As compared with the controls, the cell proliferation index was significantly reduced in both epithelial and stromal cells of the endometriotic cysts following the use of dienogest (P = 0.022 and P = 0.004, respectively). However, there was no significant difference between endometriotic cysts with and without the use of dienogest in the expressions of ER-α and PRA in the epithelial and stromal cells. Irrespective of the use of dienogest, the expression levels of ER-α and PRA in the epithelial cells were low (median: 32% and 8%, respectively). Conversely, the expression levels of ER-α and PRA in the stromal cells were well preserved (median: 68% and 92%, respectively). In the controls, there was no significant difference between endometriotic cysts in the expression levels of Ki-67, ER-α and PRA in epithelial and stromal cells during the proliferative and secretory phases. The finding of a reduction in the cell proliferation index by the use of dienogest with no change in the expressions of hormonal receptors may not support the direct progestational effect of dienogest on ovarian endometriotic cysts.

Port-site metastasis after laparoscopic surgery for mature cystic teratoma.

In this case, a 27-year-old nulliparous woman with a pelvic multiple cystic mass was treated and found with ovarian mature cystic teratoma associated with port-site metastasis (PSM). Suspecting recurrence of mature cystic teratoma, a second laparoscopic surgery found a small mass, on the right under abdomen's peritoneal membrane, at the laparoscopic port sites of the initial operation. Pathological report of the peritoneal mass and left ovarian tumor confirmed a mature cystic teratoma. To the best of the authors' knowledge, this is the first reported PSM in associated with benign ovarian tumor.

Expression of p53 in endometrial polyps with special reference to the p53 signature.

We herein examined the significance of the p53 expression in endometrial polyps (EMPs). A total of 133 EMPs, including 62 premenopausal and 71 postmenopausal women with EMP, were immunohistochemically studied for the expression of estrogen receptor (ER)-alpha, Ki-67 and p53. Apoptotic cells were identified using a TUNEL assay. A DNA sequence analysis of TP53 exons 5 to 9 was performed. Among the premenopausal EMPs, a multivariate analysis showed the labeling index (LI) for Ki-67 to correlate significantly with that for p53 (P<0.001), but not that for apoptosis. On the contrary, among the postmenopausal EMPs, the LI for Ki-67 correlated significantly with that for apoptosis (P<0.001). The p53 signature (p53S) was defined by endometrial epithelial cells, which are morphologically benign in appearance but display 12 or more consecutive epithelial cell nuclei with strong p53 immunostaining. The p53S was found in nine (12.7%) postmenopausal EMPs (mean age: 70.2 years). The median Ki-67 index for the p53S was 7%, with no significant difference from that of the glands of the postmenopausal EMPs without the p53S (P=0.058). The median apoptotic index for the p53S was 0%, which was significantly lower than that of the postmenopausal EMPs without the p53S (P=0.002). Two of four p53Ss showed TP53 mutations according to the DNA sequence analysis. The presence of the p53S is not rare in postmenopausal EMPs with an advanced age. Among postmenopausal EMPs, the LI of Ki-67 significantly correlates with that of apoptosis. However, such a positive correlation between the LI of Ki-67 and apoptosis is not observed in p53S.

Significance of p53 expression in background endometrium in endometrial carcinoma.

The p53 signature (p53S) has been proposed to be a marker of the earliest phase of development of endometrial serous carcinoma. We examined the presence of p53S in the background endometrium in cases of endometrial carcinoma. From a series of 351 endometrial carcinomas, 225 (64.1 %) lesions, for which slides of the adjacent noncancerous endometrium were available for review, were included. Expression of estrogen receptor (ER)-alpha, Ki-67, and p53 in the adjacent endometrium was studied by immunohistochemistry. The p53S was defined as the presence of morphologically benign endometrial epithelial cells with moderate to strong intensity of p53 immunostaining. Of the 225 noncancerous endometrium samples, 34 consisted of hyperplastic and 191 of non-hyperplastic endometrium. A p53S was found in 22 cases (mean age 64.2 years), 2 in hyperplastic, and 20 in non-hyperplastic background endometrium. All p53S-positive cases also expressed ER-alpha; their median Ki-67 labeling index (LI) was 4.0 % (range 0.0 to 21.0 %). The two cases with hyperplastic p53S-positive background endometrium were in association with a grade 1 endometrioid tumor in a premenopausal woman with Lynch syndrome. Of the 152 cases of endometrioid adenocarcinomas with non-hyperplastic endometrium, 12 (8 %) were p53S positive, none of which associated with EIC. Of the 21 cases of serous carcinoma, five (24 %) were p53S positive, 4 of which (19 %) associated with EIC while in 5 others (24 %) EIC was found without p53S. Of three clear cell adenocarcinomas, none were p53S positive while two contained EIC without p53S. Of 15 carcinosarcomas, 3 (20 %) were p53S positive, all of which with EIC while 6 others (40 %) were associated with EIC but without p53S. Of the 8 non-endometrioid tumors with p53S, 7 (88 %) were associated with EIC. p53S is thought to be associated with precancerous lesions of non-endometrioid tumors, including carcinosarcomas.

Prognostic significance of overexpression of p53 in uterine endometrioid adenocarcinomas with an analysis of nuclear grade.

AIM: Although overexpression of p53 is usually found in uterine serous carcinoma (USC), it is also found in some uterine endometrioid adenocarcinomas (UEA). This report describes the clinicopathological features of the UEA with overexpression of p53 with special reference to a prognostic significance of nuclear grade. MATERIAL AND METHODS: Immunohistochemical expression of p53 was examined in 322 UEA and 34 USC. Greater than 50% staining was defined as the overexpression for p53. Cox's univariate and multivariate analyses for UEA were made. RESULTS: There were 57 UEA (20.7%) showing overexpression of p53 and 31 USC (91.2%). The cancer-specific survival rate of patients with UEA without overexpression of p53, UEA with overexpression of p53 and USC was 88.2%, 76.3% and 45.7%, respectively. Univariate analyses showed overexpression of p53 to be a significant prognostic indicator in patients with UEA (P < 0.02). However, multivariate analyses for UEA showed that age, surgical stage, nuclear grade, myometrial invasion and lymphovascular space invasion were independent prognostic factors, while the significances of p53 immunoreactivity and architectural grade disappeared. In correlation between overexpression of p53 and nuclear grade, the patients with nuclear grade 1 and 2 UEA had a good prognosis, regardless of overexpression of p53. The cancer-specific survival rates of patients with nuclear grade 3 UEA with overexpression of p53 was 52.7% and was not significantly different from that of patients with nuclear grade 3 UEA without overexpression of p53 (66.7%) and USC. CONCLUSIONS: The prognostic significance of p53 immunostaining could not show in nuclear grade 3 UEA.

Expression of estrogen receptor-α as a prognostic factor in patients with uterine serous carcinoma.

OBJECTIVES: Although the expression of estrogen receptor (ER) is usually found in uterine endometrioid adenocarcinomas, it has recently been reported to be found in some uterine serous carcinomas (USCs). This report describes the clinicopathologic features of USC with an expression of ER-α, with special reference to the prognostic significance of ER-α. METHODS: The immunohistochemical expression of ER-α was examined in 33 USCs. Greater than 10% staining was defined as an overexpression of ER-α. Cox univariate and multivariate analyses for USCs were performed. RESULTS: A total of 7 USCs (21.2%) exhibited an expression of ER-α. All tumors were pure-type USCs and strongly demonstrated an overexpression of p53. The cancer-specific 5-year survival rates of patients with USC without an expression of ER-α and USC with an expression of ER-α were 54.5% and 0.0%, respectively (P = 0.04). The univariate analyses showed an expression of ER-α to be a significant prognostic indicator in patients with USC (P < 0.05). However, multivariate analyses for USCs showed that the surgical stage was an independent prognostic factor, whereas the significance of ER immunoreactivity disappeared. CONCLUSIONS: Uterine serous carcinoma with an expression of ER-α was associated with advanced-staged tumors and a significantly worse prognosis than that without an expression of ER-α. When an endometrial biopsy specimen reveals USC with an expression of ER-α and an overexpression of p53, the presence of an extrauterine lesion is suggested.

Trends in the demographic and clinicopathological characteristics in Japanese patients with endometrial cancer, 1990-2010.

OBJECTIVE: Over the past 20 years, the incidence of endometrial cancer has increased remarkably in Japan. The number of elderly females has also increased within the population of Japan. We examined the impact of advanced age on the demographic and clinicopathological characteristics in Japanese patients with endometrial cancer. METHODS: Data were collected from 319 surgically treated Japanese females with endometrial cancer from the files of the University Hospital of Occupational and Environmental Health, Yahatanishi-ku, Kitakyushu, Japan, between 1990 and 2010. χ(2) tests were performed to evaluate the trends in the variables between two decades (A: 116 cases from 1990-2000) and (B: 203 cases in 2001-2010). The histological subtypes were also evaluated based on the immunohistochemical expressions of p53, estrogen receptor, and Ki-67. RESULTS: The mean ages ± standard deviation in the decade A group and the decade B group were 57.5 years ± 9.7 years and 61.0 years ± 11.3 years, respectively (P < 0.02). There was an increase in the proportion of patients aged 70 years or older and of high-risk histological tumors including serous carcinoma, clear cell carcinoma, and carcinosarcoma (decade A group and decade B group: 9.5% vs 27.6%, P < 0.001, 10.4% vs 21.6%, P = 0.01, respectively), while the advanced surgical stage (III and IV), obesity (≥25 of body mass index), and nulliparity of the decade A group and decade B group were 23.3% vs 29.1%, P = 0.30, 28.4% vs 33.0%, P = 0.40, and 19.0% vs 21.2%, P = 0.66, respectively. The cancer-specific survival rates in the decade A group and the decade B group were 78.6% and 77.6%, respectively (P = 0.93). CONCLUSION: The increase in number of elderly females in the Japanese population is related to the increase in that of high-risk endometrial cancers. A study is needed to investigate prevention strategies and to improve the treatment of elderly patients with high-risk endometrial cancer.