Morphological demonstration of a vagal inhibitory pathway to the lower esophageal sphincter via nitrergic neurons in the rat esophagus.

BACKGROUND: The involvement of vagal parasympathetic efferents in esophageal myenteric neurons in vagal inhibitory pathways to the lower esophageal sphincter (LES) is not clear. Thus, this study was performed to demonstrate morphologically the presence of vagal inhibitory pathways to the LES via esophageal neurons. METHODS: Fast Blue (FB) was injected into the LES of Wistar rats, and 3 days after injection, the animals were subjected to electrical stimulation of the vagus nerve. The esophagus was processed for immunohistochemistry for Fos that was an immediate-early gene as a marker of neuronal activity, nitric oxide synthase (NOS), vasoactive intestinal polypeptide (VIP) and choline acetyltransferase (ChAT). The immunoreactivities were then compared with the FB labeling in esophageal neurons. KEY RESULTS: Fast Blue-labeled neurons were observed within an esophageal area of 30 mm oral to the LES, with the highest frequency in the esophagus just above the LES. Most of the FB-labeled neurons were positive for NOS and VIP, but a few for ChAT. Following vagal-electrical stimulation, one fourth of the FB-labeled neurons presented nuclei expressing Fos and most of these Fos/FB neurons were NOS-positive. CONCLUSIONS & INFERENCES: A majority of the FB-labeled esophageal neurons appeared to be descending motor neurons innervating the LES. Moreover, the colocalization of VIP and NOS in most of the LES-projecting neurons suggests that VIP and NO released from these neurons induce LES relaxation, and the innervation of the vagal efferents to the LES-projecting esophageal neurons in the distal esophagus implies a vagal inhibitory pathway responsible for LES relaxation.

Screening for cancer of the cervix with simultaneous pap smear and colposcopy. The efficacy of pap smear and colposcopy.

OBJECTIVE: Some Japanese institutes have been performing a population screening program for cervix cancer involving the simultaneous use of Pap smear and colposcopy. This program may be a good model for evaluating the efficacy of Pap smears and colposcopy. METHODS & MATERIALS: The subjects included 2,000 women who underwent primary screening at the Kanagawa Health Service Association. RESULTS: 1) The incidence of ACF (atypical colposcopic findings) was 3.6%, whereas that of abnormal Pap smears (ASC-US and above) was 1.1%; 2) Of 88 women who showed abnormal findings on Pap smear and/or colposcopy, only three cases appeared abnormal in both methods, i.e., the two methods were complementary; 3) Colposcopy was more useful for detecting mild dysplasia than the Pap smear. However, colposcopy may possibly detect benign reparatory lesions; 4) The incidence of unsatisfactory colposcopic findings (UCF) was high (24.2%), whereas no unsatisfactory cases were found by Pap smear. CONCLUSIONS: The sensitivity of the Pap smear for detecting mild dysplasia is low, whereas that of colposcopy is high. However, colposcopy may not be suitable for primary screening due to its high UCF. The low sensitivity of Pap smears may be improved by repetition or adding ancillary HPV testing.

Suppression of antibody-mediated arthritis in mice by Fab fragments of the mediating antibodies.

BACKGROUND AND PURPOSE: Fab fragments (Fabs) of antibodies maintain the ability to bind specific antigens, but lack the binding site for complement as well as the site for binding to receptors on effector cells, such as macrophages that play an important role in inflammation. In the present study, we investigated whether Fabs specific for ovalbumin (OVA) were specifically able to suppress anti-OVA antibody-mediated arthritis (AOA-MA) in mice. EXPERIMENTAL APPROACH: AOA-MA was induced by i.v. injection of purified anti-OVA antibodies into naïve mice followed by intra-articular (left ankle) challenge with the antigen. Anti-OVA Fabs prepared by digestion of anti-OVA antibodies with papain were injected i.v. immediately after administration of the intact antibodies. Normal Fabs were used as a control. Arthritis was assessed by thickness of the joints (caliper) and by histology of paw sections, stained with haematoxylin and eosin. KEY RESULTS: AOA-MA was markedly suppressed by anti-OVA Fabs, but not by control Fabs. Histologically, mice treated with control Fabs showed marked oedema of synovial tissues with a large number of inflammatory cells including neutrophils, whereas animals given anti-OVA Fabs had mild oedema of the synovium and sparse infiltration of such cells. The antigen-specific suppression of joint inflammation by anti-OVA Fabs was associated with reduced consumption of complement. In vitro studies showed that anti-OVA Fabs significantly blocked the binding of intact anti-OVA antibodies to OVA. CONCLUSIONS AND IMPLICATIONS: Antibody-mediated arthritis appears to be specifically down-regulated by Fabs that competitively inhibit the binding of antibodies to antigens.

Contrasting effects of ghrelin and des-acyl ghrelin on the lumbo-sacral defecation center and regulation of colorectal motility in rats.

BACKGROUND: We have previously demonstrated that a centrally penetrant ghrelin receptor agonist enhances colorectal motility, through activation of the lumbo-sacral defecation center (L6-S1 region of the spinal cord) in rats. In the present study, we examined the effects of the native peptide and its non-acylated counterpart in eliciting this stimulatory effect on colorectal motility. METHODS: Rats were anesthetised with α-chloralose and ketamine, and colorectal intraluminal pressure and propelled intraluminal liquid volume were recorded in vivo. KEY RESULTS: Intrathecal application of acylated ghrelin to the L6-S1 region of the spinal cord, but not intravenous application, elicited groups of phasic increases in colorectal intraluminal pressure that were associated with increased fluid output through the anal cannula. The effect was dose-dependent. The colokinetic effects of ghrelin were prevented if the pelvic nerves were severed. Reverse transcription polymerase chain reaction revealed the expression of the ghrelin and ghrelin receptor genes in the lumbo-sacral spinal cord. In contrast to acylated ghrelin, des-acyl ghrelin failed to cause changes in colorectal motility. However, when des-acyl ghrelin and ghrelin were applied simultaneously at the L6-S1 region, the ghrelin-induced enhancement of colorectal motility was significantly attenuated. CONCLUSION & INFERENCES: It is concluded that acylation of the ghrelin peptide is essential to promote propulsive contractions of the colorectum and that des-acyl ghrelin opposes this effect. At most other sites of ghrelin action, des-acyl ghrelin either has no effect or it mimics ghrelin. This is the first evidence that non-acylated ghrelin opposes the action of the acylated peptide in the spinal cord.

The oncogenic mutation in the pleckstrin homology domain of AKT1 in endometrial carcinomas.

BACKGROUND: The phosphatidylinositol 3'-kinase (PI3K)-AKT pathway is activated in many human cancers and plays a key role in cell proliferation and survival. A mutation (E17K) in the pleckstrin homology domain of the AKT1 results in constitutive AKT1 activation by means of localisation to the plasma membrane. The AKT1 (E17K) mutation has been reported in some tumour types (breast, colorectal, ovarian and lung cancers), and it is of interest which tumour types other than those possess the E17K mutation. METHODS: We analysed the presence of the AKT1 (E17K) mutation in 89 endometrial cancer tissue specimens and in 12 endometrial cancer cell lines by PCR and direct sequencing. RESULTS: We detected two AKT1 (E17K) mutations in the tissue samples (2 out of 89) and no mutations in the cell lines. These two AKT1 mutant tumours do not possess any mutations in PIK3CA, PTEN and K-Ras. INTERPRETATION: Our results and earlier reports suggest that AKT1 mutations might be mutually exclusive with other PI3K-AKT-activating alterations, although PIK3CA mutations frequently coexist with other alterations (such as HER2, K-Ras and PTEN) in several types of tumours.

Neuroendocrine features in poorly differentiated endometrioid adenocarcinomas of the endometrium.

This study aimed to clarify neuroendocrine features (NEF) in poorly differentiated (G3) endometrioid adenocarcinoma of the endometrium and to evaluate its prognostic significance. Forty cases with G3 carcinoma were investigated for NEF immunohistochemically. The histopathologic specimens were immunostained with chromogranin A, synaptophysin, and leu-7, using the labeled streptavidin-biotin method. The staining pattern was classified into diffuse, partial, or focal. The NEF was compared with clinicopathologic variables, including patients' survival. Chromogranin A was positive diffusely in 1 patient (2.5%), partially in 8 (20%), and focally in 13 (32.5%). Synaptophysin was positive diffusely in one (2.5%), partially in three (7.5%), and focally in nine (22.5%). Leu-7 was focally positive in 10 (25%) patients. The overall positive rate of the three neuroendocrine markers was 62.5%. A patient with diffusely positive staining for both chromogranin A and synaptophysin was diagnosed with neuroendocrine carcinoma. One or more neuroendocrine markers were positive in 25 cases (62.5%). Positive NEF was correlated with clinicopathologic parameters such as stage and myometrial invasion. The survival of the patients with positive NEF, especially with positive leu-7, was significantly lower than that without NEF. NEF was detected immunohistochemically in approximately 63% of the G3 carcinomas, and these patients had a poor prognosis.

Angiopoietin-1, 2 and Tie2 expressions in endometrial adenocarcinoma--the Ang2 dominant balance up-regulates tumor angiogenesis in the presence of VEGF.

We investigated Ang1, Ang2 and Tie2 expressions including balance and intratumoral vessels in the role of angiogenesis of endometrial adenocarcinoma. Immunohistochemical staining was performed on 133 patients with endometrial (endometrioid) adenocarcinoma, including 73 with G1, 34 with G2, and 26 with G3. The levels of Ang1, Ang2 and Tie2 expressions were expressed as staining score. Total vessel count (TVC), microvessel count (MVC) and mean vessel diameter (VD) in the CD34-stained tissues were measured in five hot spot areas at x 200 magnification by image cytometry. These results were compared with high and low vascular endothelial growth factor (VEGF) expressions. Ang1, Ang2, Tie2 and CD34 were expressed in the cytoplasm of tumor cells. A significant correlation was found among Ang1, Ang2 and Tie2 expressions. In high VEGF cases, Ang1 expression was correlated negatively with TVC and MVC, but positively with VD, and the Angl < Ang2 group was significantly higher in TVC and MVC and tended to be smaller in VD than the Ang1 > Ang2 group. VD was significantly larger in G3 than in G1. The Ang1 < Ang2 balance may be one of the key factors for angiogenesis of endometrial carcinoma in the presence of high VEGF expression.

Significance of p27 as a predicting marker for medroxyprogesterone acetate therapy against endometrial endometrioid adenocarcinoma.

We reported that p27 induced by medroxyprogesterone acetate (MPA) may be involved in the progestin-induced growth suppression of human endometrial adenocarcinoma cells. This study aimed at investigating whether p27 expression could be a predicting marker to evaluate the effectiveness of MPA therapy. The clinical responses of 15 patients with endometrial carcinoma treated with MPA were examined. p27 expression was evaluated by immunohistochemical staining. Percentage of positive nuclear staining was expressed as a strongly positive (SP) labeling index (LI). Before MPA treatment, SP LIs in the effective and noneffective groups were 22.6 +/- 14.3% and 9.1 +/- 9.2%. At 1-6 weeks in the MPA treatment, SP LIs increased in both groups and were significantly higher than those before the therapy. At 7-12 weeks, SP LIs in both groups decreased to the level of pretherapy. At 13-18 weeks, SP LIs in the effective group were 14.9 +/- 5.7%, whereas in the noneffective group, 1.1 +/- 2.0%. The former was significantly higher than the latter. p27 expression could predict the effectiveness of MPA treatment for endometrial carcinoma at an early stage of the 4-month period in MPA therapy and could be a useful predicting marker for MPA.

Medroxyprogesterone acetate stimulates cdk inhibitors, p21 and p27, in endometrial carcinoma cells transfected with progesterone receptor-B cDNA.

PURPOSE OF INVESTIGATION: Progestin is reported to suppress the growth of endometrial carcinomas, although its precise mechanism of action is not clear. This study aimed to transfect progesterone receptor-B (PRB) cDNA into endometrial carcinoma cells and investigate the effect of medroxyprogesterone acetate (MPA) on cell growth, and p21 and p27 expression in the transfectant. METHODS: Immunoblotting for p21 and p27 was performed at predetermined times after the administration of MPA. RESULTS: PR expression was maximally induced in Ishikawa cells at 24 hrs after the transfection. At 1 x 10(-6) M, MPA suppressed the growth of the transfectant by 34% on day 6 and stimulated p21 accumulation at 48 to 72 hrs and p27 accumulation at 48 to 96 hrs after its administration. PRB cDNA was effectively transfected and in the transfectant MPA at 1 x 10(-6) M, the dosage suppressing growth, induced p21 and p27expression. CONCLUSION: p21 and p27 may be related to progesterone-induced growth suppression in human endometrial adenocarcinoma.

Optimal dose for stage IIIB adenocarcinoma of the uterine cervix on the basis of biological effective dose.

PURPOSE: Prognosis of uterine cervical adenocarcinoma in locally advanced stage treated with radiation therapy has been considered to be much worse than that of squamous cell carcinoma because the optimal dose for the former one has not been determined. Thus, the current study was performed to investigate the optimal dose for Stage IIIB, locally advanced stage, adenocarcinoma of the uterine cervix on the basis of the biological effective dose (BED). METHODS: One-hundred and seventy-nine patients with Stage IIIB carcinoma of the uterine cervix were treated with curative intended therapy at Kitasato University Hospital between 1976 and 2000. Out of them, 13 patients had an adenocarcinoma component in pathological findings. Nine patients were diagnosed with adenocarcinoma and four patients were diagnosed with adenosquamous cell carcinoma. All patients were treated with external radiation therapy combined with intracavitary radiation therapy. The total BED10 (T-BED10) was caluculated from the BED of the external beam radiation therapy (E-BED10) plus the BED of the intra-cavitary radiation therapy (A-BED). RESULTS: Overall survival rate was 51%. Stratified by T-BED10 overall survival rate of the T-BED10 > or = 100 Gy group was 57% and that of the T-BED10 < 100 Gy group was 30%. There was a trend toward a better survival rate of the T-BED10 > or = 100 Gy group than the T-BED10 < 100 Gy group. CONCLUSION: The current study suggested that the optimal dose for Stage IIIB adenocarcinoma of the uterine cervix might be T-BED10 > or = 100 Gy.

C-kit overexpression in neuroendocrine small cell carcinoma of the uterine cervix.

PURPOSE OF INVESTIGATION: Neuroendocrine small cell carcinoma of the uterine cervix (NESCC) grows aggressively, and is resistant to anticancer agents and radiation, having an extremely poor prognosis. The incidence of c-kit proto-oncogene overexpression is high in gastrointestinal stromal tumors (GISTs) and small cell lung cancer, and tyrosine kinase inhibitors have been used effectively to treat GISTs. Few studies have investigated whether c-kit is overexpressed in NESCC. To investigate whether NESCC can be a target for molecular targeted therapy with tyrosine kinase inhibitors, we examined the expression of c-kit in this tumor. METHODS: Twenty-one NESCCs were examined for c-kit expression by immunohistochemical staining using the labeled streptavidin-biotin complex (LSAB) method. The expression of c-kit was regarded as positive (overexpression) and negative when the membrane and cytoplasm of more or less than 25%, respectively, of tumor cells were stained. RESULTS: Nine NESCCs (43%) were c-kit-positive (overexpression). No difference in age or clinical stage was noted. No difference in prognosis was observed between the c-kit-positive and -negative patients. CONCLUSION: The incidence of c-kit overexpression was high in NESCC; therefore, the patients with this tumor may become a future target for molecular-targeted therapy with tyrosine kinase inhibitors.

Clear cell adenocarcinoma of the endometrium is a biologically distinct entity from endometrioid adenocarcinoma.

Clear cell adenocarcinoma (CCA) of the endometrium has a poor prognosis, although the biologic features of this rare tumor are not clear. In this study, we analyzed the expression of biologic markers relating to carcinogenesis, tumor growth, and progression. Thirteen cases of CCA were compared with cases of endometrioid adenocarcinoma (EMA) of the endometrium. Immunohistochemical staining for p53; Ki-67; cyclins A, D1, and E; E-cadherin; progesterone receptor (PR)-A and PR-B; P-glycoprotein; MLH1; and MSH2 was performed. Labeling indices of p53, Ki-67, and cyclins A, D1, and E in CCA were 46.4 +/- 24.3%, 52.1 +/- 20.5%, 37.9 +/- 21.4%, 12.3 +/- 27.9%, and 8.2 +/- 22.9%, respectively. E-cadherin was expressed in only 1 case (7.7%) of CCA, as compared to 39 cases (61.0%) of EMA. No CCAs were positive for PR-A and PR-B. P-glycoprotein was detected in seven cases (53.8%). Loss of either MLH1 or MSH2 expression occurred in eight cases (61.5%). High-level expression of p53, cyclin A, and P-glycoprotein, and low-level or no expression of cyclin E, E-cadherin, PR-A, and PR-B was observed in CCA compared with EMA. The mechanism of cell-cycle regulation in endometrial CCA is different from that in EMA and may influence its malignant potential. Endometrial CCA is a distinct entity from EMA.

Phase II trial of docetaxel in advanced or metastatic endometrial cancer: a Japanese Cooperative Study.

The purpose of this study was to determine whether docetaxel has antitumour activity in patients with advanced or recurrent endometrial carcinoma. Chemotherapy-naïve or previously treated patients (one regimen) with histopathologically documented endometrial carcinoma and Eastern Cooperative Oncology Group performance status

Regulatory expression of lipoxin A4 receptor in physiologically estrus cycle and pathologically endometriosis.

Expression of receptors for prostaglandin (PG) and leukotriene (LT) has been reported to detect in endometrium and smooth muscle of uterus, suggesting involvement of these arachidonic metabolites in endometrial pathology and reproductive biology. Lipoxin (LX), which is produced by lipoxygenases from arachidonic acid, has been characterized as an anti-inflammatory lipid mediator. Biological actions of Lipoxin A4 (LXA4) are mediated through the specific receptor. In order to know roles of LXA4 in female genitalia, expression of LXA4 receptor mRNA was quantified by real-time polymerase chain reaction. Significantly higher expression of the receptor was detected in endometrium and myometrium than ovary in normal rats. Expression of the receptor in endometrium was increased at stage of proestrus cycle under physiological condition. Exogenous administration of progesterone into female rats significantly reduced the expression, while administration of estradiol or pregnant mare serum gonadotropin (PMSG) did not. Both, endometrium in experimental endometriosis induced in rats and the tissues from patients with ectopic endometriosis showed a higher expression of LXA4 receptor compared to the normal tissues. In contrast, expressions of BLT1 and BLT2, receptors for leukotriene B4, did not change in the endometriosis. These observations suggest a possible role of LXA4 and the receptor under physiological estrus cycle and pathological condition as endometriosis.

Small-cell carcinoma of the uterine cervix: a clinicopathologic study of 11 cases.

We report the clinical profiles and immunohistochemical features of small-cell carcinoma of the uterine cervix. Eleven cases that we have encountered at the Department of Gynecology, Kitasato University Hospital, between 1971 and 2003 are presented. Of 1370 invasive carcinomas of the uterine cervix, the incidence of small-cell carcinoma was 0.8%. Patient ages ranged between 32 and 65 years, with a mean age of 46.3 years. The clinical stages at diagnosis were Ib in four patients, IIb in three, IIIb in three, and IVb in one. All patients presented with abnormal vaginal bleeding. Two patients who are alive with no evidence of disease for 12 years and 3 years 6 months, while eight patients died of primary carcinoma between 4 and 25 months after treatment. Histopathologic findings showed solid nests with marked peripheral palisading pattern and rosette formation. Small tumor cells with scant cytoplasm demonstrated a very high nuclear/cytoplasm ratio and indistinct cell borders. The nuclei were round to oval and demonstrated increased but fine granular chromatin. Nucleoli were indistinct in all cases. Immunohistochemical findings were positive in 81.8% each for neuron-specific enolase and protein gene product 9.5, 72.7% for synaptophysin, 63.6% for chromogranin A, and 54.5% for neural cell adhesion molecule. All specimens were positive for at least one of the above. In conclusion, small-cell carcinoma of the uterine cervix revealed poor prognosis. Making an accurate diagnosis of small-cell carcinoma before performing treatment is of great significance but often difficult. Immunohistochemical analysis using several kinds of neuroendocrine markers is helpful in establishing the correct diagnosis in addition to focusing on characteristic histo- and cytopathologic features.

Lymph node pathway in the spread of endometrial carcinoma.

OBJECTIVE: To elucidate the sentinel nodes of endometrial carcinoma, the spread pathway was clarified. The correlation between lymph node spread and other clinicopathological variables was also analyzed. METHODS: Dissected lymph node samples in 342 patients who underwent pelvic and selective paraaortic lymphadenectomy were reviewed. Pelvic and paraaortic node (PLN and PAN) status was compared with clinicopathological parameters. RESULTS: Lymph node metastasis was demonstrated in 52 patients, including 46 cases with PLN metastasis and six patients with independent PAN metastasis. The metastatic sites were most frequent in the obturator and internal iliac nodes. Eleven of 49 patients who underwent PAN dissection were positive for metastasis. Sixteen of 23 cases with parametrial metastasis also metastasized in the retroperitoneal lymph node. CONCLUSION: The lymph node spread pathway in endometrial carcinoma consists of a major route via the obturator node or internal iliac node with or without parametrial involvement, and rarely a direct PAN pathway.

Cyclin D1 expression in endometrioid-type endometrial adenocarcinoma is correlated with histological grade and proliferative activity, but not with prognosis.

To elucidate carcinogenesis in the endometrium, we investigated cyclin D1 immunoreactivities in 20 normal endometria, 20 endometrial hyperplasias and 141 endometrioid-type endometrial adenocarcinoma. We also evaluated the correlation of cyclin D1 expression with Ki-67, cyclin E, cyclin A, cdk2, p27 and p53, and clinicopathological parameters and prognosis. Cyclin D1 expression increased significantly with histological grade, and the labeling index (LI) for cyclin D1 was 121 +/- 23.4% in G1, 12.7 +/- 23.7% in G2 and 15.7 +/- 18.5% in G3. The LIs were significantly correlated with those for cyclin E, cyclin A and Ki-67, but not with the LIs of cdk2, p27 or p53. In contrast, high cyclin D1 expression was significantly correlated with low p53 expression. Cyclin D1 expression was not significantly correlated with any of the clinicopathological parameters except histological grade. Cyclin D1 expression was significantly correlated with histological grade and proliferative activity, but not clinicopathological parameters and prognosis in endometrial adenocarcinoma.

Establishment and characterization of two cell lines (HEC-155, HEC-180) derived from uterine papillary serous adenocarcinoma.

Uterine papillary serous adenocarcinoma (UPSC) is an uncommon histologic subtype of endometrial cancer that characteristically behaves aggressively with a poor prognosis. We established two novel cell lines derived from UPSC designated HEC-155 and HEC-180. Both cell lines have been growing steadily in monolayer cultures for over ten years. Overexpression of p53, Ki67 and p27 was detected in both cell lines by immunohistochemistry. Using a DNA sequencing technique, a point mutation of p53 was detected in exon 8, codon 286 in HEC-155 and in exon 6, codon 195 in HEC-180. These newly established cell lines should be useful for investigating the characteristics of UPSC.

Establishment and characterization of two different types of new human endometrial adenocarcinoma cell lines (HEC-251 and HEC-265).

OBJECTIVE: Endometrial carcinomas are grouped into two types of carcinogenic entities. These two different types of cell lines designated as HEC-251 and HEC-265 were established from human endometrial adenocarcinoma. We report their characteristics. MATERIALS: HEC-251 was derived from moderately differentiated endometrioid adenocarcinoma and HEC-265 from well-differentiated adenocarcinoma. RESULTS: These cell lines grow well and serial passages can be successively carried out more than 100 times. The monolayer cultured cells reveal neoplastic and pleomorphic features, and grow in multilayers. HEC-251 cells are immuno-cytochemically positive for p53 and HEC-265 cells for PgR. Both cell lines are transplantable to nude mice and reflect the original histopathologic characteristics. CONCLUSION: The cell lines HEC-251 and HEC-265 will contribute to clarifying the characteristics of two different types of human endometrial carcinomas.

Quantitative study on the correlation between p53 gene mutation and its expression in endometrial carcinoma cell lines.

Mutant p53 protein is not degradated but accumulates in the nuclei. However, the relation between p53 gene mutation and quantity of p53 protein has not been clarified yet in endometrial carcinoma. We investigated the correlation between p53 gene mutation and its protein expression quantitatively using 11 cell lines of endometrial adenocarcinoma, endometrioid type and two serous-type cell lines. To examine p53 mutation, PCR-SSCP analysis in exon 5 to 8 and direct sequence were carried out. p53 expression was determined by immunocytochemistry and immunoblotting. The percentage of positive staining in the nuclei by immunocytochemistry was calculated as a labeling index (LI). The amount of p53 detected by immunoblotting was expressed as a comparative value of Ishikawa cells. Point mutation of p53 gene was detected in four of 11 (36.4%) cell lines of endometrioid adenocarcinoma, and all two of serous adenocarcinoma. There was a significant positive correlation between p53 LI and p53 values. The LI and the values of p53 were significantly higher in the mutant group than the wild one, thus showing a quantitative correlation between p53 protein expression and p53 gene mutation in endometrial carcinoma cell lines. It is plausible that immunohistochemical analysis of p53 could be qualified to be a convenient indicator of p53 gene mutation on clinical materials, if p53 LI is more than 40 (M-SD in mutant p53).