Arterial oxygenation can fall critically during intramedullary nailing of pathological femoral fractures.

BACKGROUND: The intramedullary nailing of a femoral shaft metastatic fracture or an impending fracture has been complicated by hemodynamic accidents in up to 13% of patients. In previous studies, otherwise healthy patients pulled well through the nailing despite high pulmonary shunting and vascular tone and right ventricular strain. We hypothesized that unfavorable hemodynamic and oxygenation trends milder than catastrophic ones can be found intraoperatively in most patients with a pathological fracture and cancer-affected lungs. METHODS: Eleven patients with a femoral metastatic fracture or an impending fracture were studied in general anesthesia. Radial artery and fast-response pulmonary artery catheters were inserted. Pre-, intra-, and postoperatively, 26 variables were measured and/or calculated up to 20 hours. Reamed nailing with a gamma nail was performed. RESULTS: At awake baseline, the mean pulmonary arterial pressure was 20 mm Hg ± 7 mm Hg and the shunt flow was 19% ± 6%. As response to the nailing, shunting increased from 14% ± 7% (mechanically ventilated) to 23% ± 10% (p < 0.05), and mean pulmonary arterial pressure increased to 29 mm Hg ± 6 mm Hg (p < 0.001). Oxygenation deteriorated to a level typical of acute lung injuries (Pao2/FIO2 242 mm Hg ± 73 mm Hg; p < 0.05). Intraoperatively, the oxygen delivery was poor, and acidosis developed (base excess, -2.9, p < 0.05). CONCLUSION: The baseline condition of patients with a pathological femoral fracture was comparable with that of healthy patients subjected to femoral fracture surgery. After reaming, arterial oxygenation deteriorated, being clinically poor for the rest of the study. We suggest increased inspiratory oxygen concentration intra- and postoperatively and maintenance of oxygen delivery by transfusions as needed, especially because hypoxia stimulates the growth of cancer.

Matrix metalloproteinase (MMP)-7 in salivary gland cancer.

INTRODUCTION: High levels of certain matrix metalloproteinases (MMPs) have been detected in various human cancers. The purpose of this study was to analyze the expression of MMP-7 in salivary gland cancer (SGC) by immunohistochemistry and to associate the results with the clinical data and the 10-year survival of the SGC patients. MATERIAL AND METHODS: Immunohistochemistry for MMP-7 was performed in a series of 107 paraffin-embedded sections of SGC. The samples represent the entire SGC population in Finland from 1991-1996. Mortality follow-up ended December 31, 2006. RESULTS: The study population of 107 patients consisted of 47 male and 60 female subjects, ranging in age at the time of diagnosis between 23 and 90 years. The minimum follow-up time was 10.6 years and the maximum 15.9 years. By age-adjusted analysis lower staining intensity was associated with worse overall survival of patients with acinic cell carcinoma (p = 0.047, HR 6.5, 95% Cl 1.0-41.7) and in mucoepidermoid carcinoma (p = 0.010, HR 9.3, 95% CI 1.7-50.0). Low staining intensity was also associated with worse disease-specific survival of patients with acinic cell carcinoma (0-1 vs. 2-3; p = 0.047, HR 13.7, 1.0-200.0). VCI Ki-67 was an important prognostic factor for survival of the entire data set (p < 0.0001, HR 4.7, 95% Cl 2.3-9.8). CONCLUSIONS: MMP-7 is associated with the prognosis of patients with acinic cell and mucoepidermoid carcinoma.

Expression of matrix metalloproteinase-1, -7, -9, -13, Ki-67, and HER-2 in epithelial-myoepithelial salivary gland cancer.

BACKGROUND: The expression of matrix metalloproteinases (MMPs) in epithelial-myoepithelial salivary gland carcinoma has not been studied previously. METHODS: Immunohistochemistry for MMP-1, -7, -9, -13, Ki-67, and HER-2, as well as HER-2 gene amplification by silver enhanced in situ hybridization was performed in a series of 12 paraffin-embedded histopathologic samples of patients from Canada and Finland. RESULTS: A positive MMP-13 (p = .0022), higher MMP-13 (p = .0274), and higher MMP-9 (p = .0274) index (multiplication of staining intensity by percentage of the positive cells) predicted better overall survival. In disease-specific analysis, higher MMP-9 index (p = .0327) predicted better survival. A higher volume corrected index (VCI) of Ki-67 (p = .0339) predicted worse disease-specific survival. In 1 patient, HER-2 oncogene amplification was observed. CONCLUSION: MMPs and Ki-67 may have prognostic impact in epithelial-myoepithelial carcinoma.

Lower recurrence risk through mammographic screening reduces breast cancer treatment costs.

Mammographic screening is associated with a reduced risk of breast cancer recurrence. The objective of the study was to evaluate treatment costs due to breast cancer recurrence in relation to patients' use of mammographic screening, consecutively collected in a defined population. The study included 418 women exposed to screening and 109 women unexposed to screening diagnosed with stage I-III breast cancer. During the first eight years after primary diagnosis, 19% (N=80) of the exposed women and 33% (N=36) of the unexposed women developed recurrent disease, P=0.002. In the exposed group, 41% of the 8-year treatment costs were for the treatment of patients who developed recurrent disease, compared with 52% in the unexposed group, P=0.039. Among the relapsed patients, the mean post-recurrence costs were EUR14,950, accounting for 65% of their total 8-year costs. The mean post-recurrence costs were comparable for both exposure groups irrespective of the detection method.

Matrix metalloproteinase (MMP)-1, -9 and -13 as prognostic factors in salivary gland cancer.

CONCLUSIONS: In the current study matrix metalloproteinases (MMPs)-9 and -13 were associated with the prognosis in salivary gland cancer (SGC), indicating that they contribute to the progression and invasion of these malignant tumours. OBJECTIVES: Elevated levels of certain MMPs have been detected in various advanced human cancer types. The purpose of the study was to analyse the expression of MMP-1, -9 and -13 in SGC by immunohistochemistry and correlate the results to the clinical data and 10-year survival of SGC patients in a nationwide material. MATERIALS AND METHODS: Immunohistochemistry for MMP-1, -9 and -13 was performed in series of 103 paraffin-embedded sections of SGC. RESULTS: High MMP-13 staining intensity predicted poor survival (3 vs 1; p=0.08) in the whole material studied. High MMP-13 intensity (2+3 vs 1; p=0.05), percentage (2 vs 1; p=0.03) and index (3 vs 1; p=0.02) were associated with poor survival in acinic cell carcinoma. However, high MMP-9 index in adenoid cystic carcinoma (p=0.06) and the percentage of positively staining cells in salivary duct carcinoma patients (p=0.05) was associated with poor survival. High MMP-1 staining intensity (2 vs 0; p=0.06) and index (% x intensity); (2 vs 1, p=0.04) were associated with better overall survival in the whole material.

Morphometric analysis using automated image analysis of CD34-positive vessels in salivary gland acinic cell carcinoma.

CONCLUSIONS: In computer-assisted analysis of acinic cell cancer (ACC) morphological characteristics of CD34 immunoreactivity were detected. Bigger vessel size, vessel irregularity, and lower intensity of CD34-positive vessel staining may indicate unfavorable prognosis. OBJECTIVES: Salivary gland cancer (SGC) is a morphologically diverse group of malignancies, the most common histological types being mucoepidermoid, adenoid cystic and ACC, which has the most favorable prognosis of the three. The aim of this research was to study the applicability of automated image analysis as prognostic criteria in ACC. PATIENTS AND METHODS: In a nationwide study covering SGC patients in Finland during 1991-1996, 34 patients with ACC (15 males, 19 females, aged 19-95 years, mean 55 years) were included. Parameters were measured from CD34-stained samples. RESULTS: In all, 10 385 vessels were measured, of which 9873 were from specimens from patients who were alive 5 years after treatment (n=32, group I) and 512 were from patients who died of disease (n=2, group II). The following results were found in group II versus group I: mean vessel size 469 microm vs 272 microm (p=0.024); vessel irregularity 28.3 microm vs 22.3 microm (p<0.001); CD34 staining intensity 0.555 microm vs 0.584 microm (p=0.024).

Ultrasonographic-guided pervaginal cul-de-sac cytology in the follow-up of ovarian carcinoma.

UNLABELLED: The aim of this study was to compare, prospectively, traditional pervaginal cul-de-sac aspiration cytology with an ultrasonographic-guided aspirate in the detection of residual or recurrent ovarian carcinoma. PATIENTS AND METHODS: Fifty-one patients with ovarian carcinoma were monitored during chemotherapy (21 patients) or follow-up (30 patients) after first-line treatment. All patients underwent both traditional blind pervaginal cul-de-sac aspiration cytology and an ultrasonographic-guided pervaginal aspirate. The samples were classified as class 0 or insufficient when no mesothelial cells were detected in the aspirate. The results of cytological classification of the aspirates were compared with each other according to sampling order. RESULTS: Samples were classified as class 0 in 56% when the traditional cul-de-sac aspiration was taken first, and in 73% when ultrasonographic-guided aspiration was taken first (p = 0.249, Fisher's exact test). The number of class 0 samples was smaller among those taken second than among those taken first (22 (44%) vs. 33 (65%), p = 0.046). Four recurrences were detected during the mean follow-up of six months (range 2-11 months) in 30 patients who were followed-up after the first-line treatment. In one case, a positive cul-de-sac cytology was the first and only early indication of recurrence. CONCLUSION: The use of ultrasonography did not improve the accuracy of the cul-de-sac aspiration. The greater amount of fluid in the cul-de-sac during the second sampling might contribute to achieving a better result.

Prognostic significance of Ki-67 and p53 as tumor markers in salivary gland malignancies in Finland: an evaluation of 212 cases.

The proliferative capacity of a tumor as measured by Ki-67 nuclear antigen is one of the most powerful indicators of tumor behavior. Ki-67 is considered a useful tool in determining the aggressiveness of malignant neoplasms. p53 tumor suppressor gene mutations have been linked with the development and progression of a number of various cancer types. p53 tumor suppressor protein and the volume corrected index of Ki-67 corresponding to Ki-67 /mm2 of tumor tissue (VCI Ki-67) in salivary gland tumors were evaluated by immunohistochemistry from paraffin embedded sections in a series of 212 patients. The follow-up time in this nationwide full population-based study was up to five years. The association of clinicopathological features and the results of present study with survival were examined. In multivariate analysis high VCI Ki-67 was associated with worse survival of SGC patients (p = 0.0114). Supplementary information was brought by age (p = 0.0002), lymph node status (p = 0.0014), gender (p = 0.0017) and stage (p = 0.0191). p53 expression did not have additional value in prediction of survival (p = 0.1433) compared to the commonly clinical used parameters. In this material consisting of various salivary gland carcinomas VCI Ki-67 was a good prognostic factor for survival.

Population-based mammography screening results in substantial savings in treatment costs for fatal breast cancer.

AIMS: The aim was to assess the effect of population-based mammography screening on treatment costs for fatal breast cancer in Turku, Finland. MATERIALS AND METHODS: The study included 556 women with invasive breast cancer, diagnosed at the age of 40-74 years in 1987-1993: 427 in the screened group (screen-detected or interval cancer) and 129 in the unscreened group (not yet invited or refused screening). Both groups were followed up for 8 years from diagnosis. RESULTS: In the unscreened group, 32 (25%) patients died of breast cancer versus 49 (12%) in the screened group (p < 0.001). The non-discounted mean treatment costs were 2.8-fold for those dying of breast cancer compared to survivors: 26,222 euros versus 9,434 euros; the difference between means was 16,788 euros (95% CI 14,915-18,660) (p<0.001). The mean costs for fatal cases were high, irrespective of the way cancer was detected: 23,800 euros in the unscreened group versus 27,803 euros in the screened group; the difference between means was -4,003 euros (-10,810 to 2802) (p=0.245). In the unscreened group, patients with fatal breast cancer accounted for 41% (0.76/1.87 million euros) of the total treatment costs versus 29% (1.36/4.76 million euros) in the screened group. It was estimated that about one third of costs for fatal breast cancer were avoided through mammography screening, accounting for 72-81% of the estimated total treatment cost savings achieved by screening. About 31-35% of the screening costs for 1987 to 1993 were offset by savings in treatment costs. CONCLUSIONS: Treatment costs for fatal breast cancer are high. Mammography screening results in substantial treatment cost savings, in which reduction of fatal disease is the key element.

Salivary gland cancer in Finland 1991--96: an evaluation of 237 cases.

CONCLUSION: In this material consisting of various salivary gland carcinomas, stage I, male gender and age were the most powerful predictors of patient outcome. OBJECTIVES: To retrieve the records of all salivary gland cancer (SGC) patients diagnosed in Finland between 1991 and 1996 and to evaluate the incidence, histological type and location of SGC, the treatment given and the outcome. MATERIAL AND METHODS: The records for all SGCs (n =286) diagnosed in Finland between 1991 and 1996 and reported to the Finnish Cancer Registry were retrieved. The histological re-evaluation and retrospective study involved 237 SGC patients. RESULTS: The study population consisted of 125 males and 112 females. The mean age was 59 years (males 61 years, females 58 years). Follow-up was at least 5 years. The commonest tumor location was the parotid gland (n = 152; 64%), followed by the minor salivary glands (n =46; 19%), the submandibular gland (n =38; 16%) and the sublingual gland (n = 1; 0.4%). The most frequent histological types of SGC were adenoid cystic carcinoma (n =65; 27%), mucoepidermoid carcinoma (n =45; 19%) and acinic cell carcinoma (n =41; 17%). Surgery, either alone or in combination with other treatment modalities, was used in 209 cases (88%). Radiotherapy was given to 136 patients (57%), 13 of whom (5%) did not undergo surgery. The 5-year overall survival rate was 56.5%, and for stages I-IV it was 78%, 25%, 21% and 23%, respectively (p <0.001; log-rank test). Of the commonest tumor types, the best 5-year relative survival rate was for patients with acinic cell carcinoma (96%), followed by those with mucoepidermoid (79%) and adenoid cystic carcinoma (74%).

Mammographic screening reduces risk of breast carcinoma recurrence.

BACKGROUND: The current report is a long-term evaluation of breast carcinoma recurrence, factors predicting recurrence, and postrecurrence prognosis in relation to patients' use of service screening, which has been provided in Turku, Finland, since 1987 for women ages 40-74 years. METHODS: The current study included 527 invasive breast carcinomas: 418 in the screening group (which included screen-detected and interval malignancies) and 109 in the nonscreening group (which included breast carcinomas detected before initial screening and those detected in patients who chose not to undergo screening). These breast carcinomas were diagnosed among women ages 40-74 years between 1987 and 1993, with follow-up extending until the end of 2001. RESULTS: In the screening group, the risk of recurrence was only approximately half of the corresponding risk in the nonscreening group (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.39-0.83; P = 0.003). Five years after the primary diagnosis, 16% of patients in the screening group and 28% of patients in the nonscreening group (P = 0.001) had experienced recurrence; 10 years after diagnosis, the corresponding rates were 21% and 34%, respectively (P = 0.001). Postrecurrence prognosis was comparable for both detection groups (HR, 1.17; 95% CI, 0.70-1.94; P = 0.551), with approximately half of all patients dying of disease 5 years after recurrence. Detection of breast carcinoma via a method other than mammographic screening was associated with a high risk of recurrence on univariate analysis. On Cox multivariate analysis, risk factors for recurrence included lobular histologic type (HR, 2.23; 95% CI, 1.44-3.48; P < 0.001), poor histologic grade (HR, 2.02; 95% CI, 1.20-3.39; P = 0.008), and large tumor size (HR, 1.60; 95% CI, 1.07-2.37; P = 0.021). CONCLUSIONS: Long-term data from a population-based program demonstrated that mammographic screening reduced patients' risk of breast carcinoma recurrence. Specifically, the risk for patients with screen-detected disease was only approximately half of the risk for patients with non-screen-detected disease. Nonetheless, postrecurrence prognosis was comparable for patients in both detection groups.

Lower costs of hospital treatment of breast cancer through a population-based mammography screening programme.

BACKGROUND: The objective of this study was to evaluate the hospital treatment costs of invasive breast cancer in relation to the mode of detection, i.e. by mammography screening, between screenings or without screening during a population-based mammography screening programme, which started in 1987 among 36,000 women aged 40 to 74 years in the city of Turku, Southwest Finland. METHODS: The treatment costs and survival days of 556 women diagnosed with invasive breast cancer at the age of 40 to 74 years in 1987 to 1993 were followed up for five years from diagnosis or until death, whichever occurred first. RESULTS: Screen-detected cancers had the lowest average costs. The mean treatment costs per patient were 1.4-fold for clinical cancers and 1.3-fold for interval cancers compared to screen-detected cancers (p<0.001). The corresponding ratios in the mean treatment costs per survival day were 3.5 for clinical cancers and 1.9 for interval cancers (p<0.001). The mean treatment costs per patient were 1.3-fold for the non-screened group (clinical cancers) compared to the screened group (screen-detected and interval cancers) (p<0.001). The corresponding ratio was 3, when the mean treatment costs per survival day were compared (p<0.001). The estimated savings resulting from early treatment were 26-30% measured as a proportion of the screening costs for 1987 to 1993. CONCLUSION: The treatment costs of screen-detected cancers are lower than those of cancers detected by other methods. The study shows the potential for reducing treatment costs through early detection of breast cancer by mammography screening.

Characterization of 10 vulvar carcinoma cell lines by karyotyping, comparative genomic hybridization and flow cytometry.

OBJECTIVE AND METHODS: Ten vulvar squamous cell carcinoma cell lines established at the University of Michigan (UM-SCV-1A, -1B, -2, -3, -4, -6, -7) and at the University of Turku (UT-SCV-1, -2, -3) were characterized by G-banding karyotyping, comparative genomic hybridization (CGH), and deoxyribonucleic acid (DNA) flow cytometry. RESULTS: All cell lines had hyperdiploid DNA content as measured by flow cytometry. The DNA index (DI) remained relatively stable through different passages in 9 of 10 cases. DIs of UM-SCV-3 and UT-SCV-2 were near-diploid, as were the corresponding karyotypes. The 10 SCVs showed remarkable genetic similarities with respect to consistent chromosome rearrangements. Loss of 3p, noted in 8/10 SCVs, was narrowed to the smallest common region at 3p11-3p13. Loss of 8pter-p11 was observed in 10/10 cell lines. Loss of 11qter-q23 was present in UM-SCV-1 and -2, and in all four recently karyotyped SCVs. Other consistent losses include Xpter-p11 in 6/10, and 18qter-q11 in 7/10 cell lines. Common gains included gain of 8q in 8/10 and 3q in 6/10. Consistent copy number imbalances were confirmed by CGH; concerning loss of 3p, in 63%, to loss of 8p in 70%, to gain of 3q in 83%, and to gain of 8q in 75% of the cell lines. CONCLUSIONS: CGH and karyotyping showed concordance in defining copy number imbalances, thus supporting the accuracy of CGH to detect chromosome imbalances in tumors that cannot be karyotyped.

Significant improvement in breast cancer survival through population-based mammography screening.

The purpose of this study was to evaluate the effect of population-based mammography screening on survival. A total of 176 908 screening examinations were performed in 36 000 women aged 40-74 during the years 1987-1997. Screen-detected and interval primary invasive breast cancers (n=685, screened) were more often smaller (P<0.0001), localised (P<0.0001) and histologically better differentiated (grade I vs II-III, P<0.0001) than pre-screening cancers and cancers detected after the defined interval from the last screening (n=184, clinical). Survival was far better in the "screened" group than in the "clinical" group (P<0.0001, HR 2.55; CI 95% 1.77-3.67). Cox's multivariate analysis revealed axillary lymph node negativity (P<0.0001), histological grade I (P=0.0005) and size less than or equal to 20mm (P=0.0118) as explanations of the beneficial effect of screening. A new observation we recorded was that screening had a beneficial effect even in women whose cancer had already spread into the axillary lymph nodes.

Response of estrogen receptor-positive intraabdominal fibromatosis to aromatase inhibitor therapy.

BACKGROUND: Intraabdominal fibromatosis is a rare tumor-like lesion of uncertain etiology. CASE: A 49-year-old woman underwent abdominal hysterectomy and bilateral salpingooophorectomy in 1997 to treat uterine leiomyomata and ovarian fibromatosis. Postoperatively, she received estradiol 2 mg daily as hormone replacement therapy (HRT). In 2000, laparotomy performed for a large pelvic tumor revealed inoperable intraabdominal fibromatosis. The tumor, which was positive for estrogen and progesterone receptors, resolved during aromatase inhibitor therapy. The first follow-up computed tomographic (CT) scan revealed that the tumor masses were significantly reduced in size, and successive CT scans revealed stable disease. CONCLUSION: Intraabdominal fibromatosis that expresses estrogen and progesterone receptors may respond favorably to treatment with aromatase inhibitors.

Metalloelastase (MMP-12) expression by tumour cells in squamous cell carcinoma of the vulva correlates with invasiveness, while that by macrophages predicts better outcome.

Human metalloelastase (MMP-12) has been implicated in elastin degradation and macrophage migration in many pathological conditions. It also generates angiostatin, thus having a potential to prevent tumour angiogenesis. It has previously been shown that transformed epithelial cells express MMP-12 in skin cancer. The aim of this study was further to elucidate the role of metalloelastase in squamous cell cancer (SCC) progression. By in situ hybridization, expression of MMP-12 mRNA was detected in 28/33 vulvar SCC samples in CD-68-positive macrophages, while 10 samples had positive cancer cells. By immunohistochemistry, MMP-12 protein was seen in the same area as the mRNA. MMP-12 mRNA expression in tumour cells correlated with more aggressive histology (p = 0.0099). In contrast, macrophage-derived MMP-12 mRNA was more abundant in well-differentiated grade I than grade III tumours (p = 0.01). However, the level of MMP-12 mRNA, regardless of its origin, did not correlate with metastasis or patient survival. No significant correlation was found between macrophage-derived MMP-12 mRNA and a low amount of blood vessels, as quantitated after von Willebrand staining. In agreement with vulvar SCCs in vivo, MMP-12 was expressed in cultured SCC cells by northern and western blot analysis. In HaCaTs and epithelial MCF-10f cells, MMP-12 mRNA was induced by transforming growth factor-beta1 (TGF-beta1) and tumour necrosis factor-alpha (TNF-alpha) as measured by quantitative RT-PCR (TaqMan). Two MMPs capable of generating angiostatin in vivo, matrilysin (MMP-7) and gelatinase B (MMP-9), were also examined in these tumours. MMP-7 mRNA was mainly expressed by epithelial tumour cells, particularly in less differentiated tumours. MMP-9 was usually expressed by neutrophils and macrophages; epithelial protein was predominantly found in grade II/III tumours. These results suggest a dual role for MMP-12 in tumour progression.

Paclitaxel combined with fractionated radiation in vitro: a study with vulvar squamous cell carcinoma cell lines.

Concurrent paclitaxel and radiation has given promising results in the treatment of a variety of solid tumors. We wanted to test the efficacy of this combination for vulvar carcinoma, which currently has a poor outcome in advanced stages. The radiation sensitivity, sublethal damage repair (SLDR) capacity and effect of paclitaxel during fractionated radiation were assessed in our study on 7 vulvar inherently radioresistant squamous cell carcinoma (SCC) cell lines. The 96-well plate clonogenic assay was used. Survival data were fitted to the linear quadratic model. The area under the curve (AUC), equivalent to mean inactivation dose (D), was obtained with numerical integration. AUC ratios between single-dose radiation and fractionated radiation with or without paclitaxel were used to determine the SLDR of the cell lines and the effect of paclitaxel on it. Seven currently tested vulvar SCC cell lines were found to have a limited capacity of repairing sublethal damage (SLD). Only 3 of them presented SLDR of significance. The effect of concurrent radiation and paclitaxel was clearly additive when the radiation dose was fractionated in most of the cell lines. In addition, 2 of the cell lines having SLDR exhibited a trend toward losing the repair capacity when paclitaxel was present during the irradiation. In addition, the survival curve of the UM-SCV-1A cell line gave the impression of a true paclitaxel effect on SLDR. Paclitaxel used concurrently with fractionated radiation showed effectiveness on vulvar carcinoma. The effect was at least additive and could even be expected to abrogate the SLDR during split-dose radiation.

The expression of cyclooxygenase-1 and -2 in proliferative endometrium and endometrial adenocarcinoma.

BACKGROUND: The activity of cyclooxygenase-2 (COX-2) is increased in inflammation and in several cancer types. We investigated the expression of COX-2, cyclooxygenase-1 (COX-1), nitric oxide synthase-2 (NOS-2) and nitric oxide synthase-3 (NOS-3) in normal proliferative and secretory human endometrium, and in endometrial adenocarcinoma. METHODS: Human endometrium was collected at hysterectomy. Seven samples were in proliferative and 11 samples in secretory stage. Twelve specimens from endometrial carcinoma were collected, as well. Immunohistochemistry was used to investigate the expression of COX-1, COX-2, NOS-2 and NOS-3. RESULTS: COX-2 immunostaining was detected in most specimens of normal proliferative glandular epithelium (86%) and of endometrial carcinomas (92%). COX-2 staining was often detected in cancer cells on the border areas of the tumour and on the areas of invasive growth. Staining for COX-2 was seen in proliferative glands usually only in the basal layer of the endometrium. NOS-2 was usually absent or negligible in proliferative endometrial glands and also in the cancer cells of endometrial adenocarcinomas. No staining for either COX-2 or NOS-2 was seen in specimens of secretory glandular epithelium. The expression of the constitutive COX-1 and NOS-3 was negligible or weak in the glandular epithelium of proliferative and secretory endometrium and in endometrial cancer cells. CONCLUSIONS: The expression of the inducible COX-2 but not of COX-1 is stimulated in the glandular epithelium of proliferative endometrium and in the cancer cells of human endometrial adenocarcinoma, in particular in those in the borders of carcinoma and spreading into lymphatic vessels.