Prostate cancer epidemiology in a rural area of North Western Greece.

Epirus is a rural area of North-Western Greece. We reviewed data from 4 hospitals for 4.975 patients who underwent prostate biopsy in Epirus in the twelve year period from 1999 to 2010. Two six-year periods were compared (1999-2004 and 2004-2010). All cases of prostate cancer confirmed by biopsy were recorded and age-standardized incidence rates per 100,000 males were calculated. We also recorded the clinical stage for patients diagnosed in our hospital and correlated this with PSA and Gleason scores. Percentage of positive prostate biopsies was also calculated. There were a total of 1714 new cases during 1999-2010 and the mean annual age-adjusted incidence was 34/100,000. The mean incidences during 1999-2004 and 2005-2010 were 26/100,000 and 42/100,000, respectively. The mean age at diagnosis was 74. The most common Gleason score was 6 and the prevalent clinical stage was T2. Median PSA at diagnosis was 10.8 ng/ml. There was a significant difference between stage cT4 and all other stages regarding PSA value (p=0.000). A positive correlation was found between Gleason score and PSA (p=0.013). These results are in accordance with the incidence rise recorded in neighboring countries of South-East Europe. However we should keep in mind the risk of overdiagnosis and the detection of low-risk cancers that would not have caused morbidity or death during a man's lifetime anyway.

Angiomyofibroblastoma of the vagina in a postmenopausal breast cancer patient treated with tamoxifen: clinicopathologic analysis of a case and review of the literature.

Angiomyofibroblastoma is a rare mesenchymal tumor. This study presents the clinical, histologic, and immunohistochemical features of an angiomyofibroblastoma of the vagina occurring in an 80-year-old breast cancer patient under prolonged treatment with tamoxifen. Histologically, the tumor was characterized by alternating hypercellular and hypocellular edematous zones and small- to medium-sized blood vessels, which were characteristically thin walled. The tumor cells were spindle shaped (mainly) or round shaped (occasionally) arranged in cords and nests. The stroma was edematous and contained inflammatory cells, especially lymphocytes and mast cells. Immunohistochemistry of the tumor cells revealed diffuse and intense immunoreactivity for vimentin and desmin. The staining for estrogen receptors and progesterone receptors was positive, with a percentage of 70% and 40%, respectively. In conclusion, the tumor was diagnosed as an angiomyofibroblastoma based on its typical histologic and immunohistochemical features. The expression of estrogen and progesterone receptors suggests that it might arise as a neoplastic proliferation of hormonally responsible mesenchymal cells. Tamoxifen may exert stimuli effects upon mesenchymal cells.

Aggressive angiomyxoma of the vulva: our experience of a rare case with review of the literature.

Aggressive angiomyxoma is a rare, benign but locally aggressive mesenchymal neoplasm, which occurs almost exclusively during the reproductive years of women. A 28-year-old woman developed an aggressive angiomyxoma within the left labium minus of the vulva. The tumor was excised, but the lesion was expanded to the surgical margins. Microscopically, sections showed many walled vessels of various sizes, a loose myxoid and collagenous stroma and stellate and spindle-shaped neoplasmatic cells. Immunohistochemically, the neoplasmatic cells showed strong positivity for vimentin and desmin and moderate positivity for CD34 and estrogen receptors. In conclusion, aggressive angiomyxoma of the vulva should be distinguished from the benign and malignant myxoid tumors or tumor-like conditions of vulva. The pathologic and immunohistochemic characteristics, the difficulties in determining the surgical margins and the treatment of this tumor are discussed. Also, the international literature is reviewed.

Expression of the cell-cycle regulatory proteins (cyclins D1 and E) in endometrial carcinomas: correlations with hormone receptor status, proliferating indices, tumor suppressor gene products (p53, pRb), and clinicopathological parameters.

PURPOSE OF INVESTIGATION: This study aimed to investigate the immunohistochemical expression of cyclins D1 and E in normal, hyperplastic and neoplastic endometrium, and their correlation with proliferative activity and clinicopathological features. METHODS: We carried out immunohistochemical techniques on archived material of formalin-fixed paraffin-embedded tissues using the antibodies against the cyclins D1 and E, PR-ER, p53, Ki67 (MIB1) and pRb with the streptavidin-biotin-peroxidase method in a total of 20 cases of normal endometrium, 32 cases of hyperplastic endometrium and 66 cases of endometrial carcinomas. RESULTS: Cyclin D1 and E immunoreactivity was observed in the nuclei of tumour cells in 18.2% and 39.1%, respectively, of the cases of endometrial carcinomas. Cyclin D1 labelling index was not significantly correlated with any of the clinicopathologic parameters examined. However, there was a significant correlation between the cyclin E labelling index and histological grade of carcinoma (p = 0.00096), which increased significantly with histological grades of malignancy. We also detected a significant correlation between cyclin E and PCNA (p < 0.0001) as well as with the tumor suppressor genes p53 and pRb (p = 0.052 and 0.0002, respectively) in endometrioid endometrial carcinoma. CONCLUSION: Our results indicate that cyclin E overexpression may be involved in the development and/or proliferation and differentiation of human endometrioid endometrial carcinoma. Immunoexpression of cyclin D1 does not appear to be associated with cell-cycle progression in the benign or malignant endometrium.

Isolated torsion of the fallopian tube: a case report and review of the literature.

INTRODUCTION: Isolated torsion of the fallopian tube is a very rare condition. It occurs without ipsilateral ovarian involvement associated with pregnancy, haemosalpinx, hydrosalpinx, ovarian or paraovarian cysts and other adnexal alterations or even with an otherwise normal fallopian tube. We document a case of isolated torsion of the right fallopian tube associated with hydrosalpinx. CASE: The patient was a 39-year-old female, para 2, gravida 4, who was presented with acute pelvic pain, nausea and vomiting. Her medical history included an appendectomy and right hydrosalpinx diagnosed five months before admission by hysterosalpingography because of investigation for secondary infertility. The urinary pregnancy test was negative. Pelvic ultrasonography showed a dilated folded right tubular structure measuring 7.8 x 2.7 cm with thickened echogenic walls and mucosal folds protruding into the lumen; the ovaries and uterus were unremarkable. No free fluid in the cul-de-sac was noted. Preoperatively, a diagnosis of twisted right fallopian tube was suspected and an exploratory laparotomy confirmed the diagnosis of isolated torsion of the oviduct. The ipsilateral ovary appeared normal, but the fallopian tube was gangrenous and right salpingectomy was performed. The patient became pregnant three months after surgery. CONCLUSION: Isolated torsion of the fallopian tube should be considered in the differential diagnosis of patients with acute abdomen and previous medical history of hydrosalpinx.

Expression patterns of cyclins D1, E and cyclin-dependent kinase inhibitors p21(Waf1/Cip1) and p27(Kip1) in urothelial carcinoma: correlation with other cell-cycle-related proteins (Rb, p53, Ki-67 and PCNA) and clinicopathological features.

INTRODUCTION: The expression pattern of cyclins D1 and E, as well as cyclin-dependent kinase inhibitors p21(Wa1/Cip1) and p27(Kip1) and their relationship to tumour behaviour and patients' prognosis was examined in 142 urothelial cell carcinomas. The expression of these proteins was also analyzed along with other cell-cycle-related proteins such as: p53, pRb and the proliferation-associated indices Ki-67 and proliferating cell nuclear antigen (PCNA). PATIENTS AND METHODS: These molecule markers were localized immunochemically using the monoclonal antibodies anti-cyclin D1 (DCS-6), anti-cyclin E (13A3), anti-p21 (4D10), and anti-p27 (1B4) in 142 patients with urothelial cell carcinoma. RESULTS: Focal positivity (<10% of tumour cells) or the absence of cyclin D1 immunostaining was observed in 105/142 (73.9%) of the tumours. Cyclin D1 expression was correlated with tumour grade and stage as well as with the existence of in situ component. In addition, cyclin D1 expression was positively correlated with p21(Waf1/Cip1) and p27(Kip1) and inversely with the Ki-67 score. Focal positivity (<20% of tumour cells) or the absence of cyclin E immunoreactivity was observed in 105/142 (73.9%) in all cases. Cyclin E expression was correlated with tumour stage. A positive relationship between cyclin E expression and the two associated proliferating indices Ki-67 and PCNA, as well as with p53 and p27(Kip1) proteins expression was noted. Absence or focal positivity (<5% of tumour cells) of p21(Waf1/Cip1) was detected in 88/142 (62%) of the carcinomas. p21(Waf1/Cip1) expression was correlated with tumour grade and stage. A positive relationship of its expression cyclin D1, cyclin E, p27 and pRb expression was observed. Absence or focal immunostaining (<20% of tumour cells) of p27 protein was detected in 55/141 (39%) in all cases. p27(Kip1) expression was correlated with tumour grade as well as with cyclins D1 and E. The prognostic significance of cyclins D1, E and cyclin-dependent kinase inhibitors p21(Waf1/Cip1), p27(Kip1) in determining the risk of recurrence and progression with both univariate (log rank test) and multivariate (Cox regression) methods of analysis showed no statistically significance differences. CONCLUSION: These findings suggest that the level of the cell cycle regulators studied does not seem to have a clinical value in terms of predicting the risk of early recurrence and progression. In addition the interrelationship probably means their contribution to the regulation of cell growth through different pathways in bladder carcinogenesis.

Primary postpartum haemorrhage due to a large submucosal nonpedunculated uterine leiomyoma: a case report and review of the literature.

The complications of leiomyomas during pregnancy are very rare and can be divided into those occurring during pregnancy, at delivery and in puerperium. We present an unusual complication of large submucosal nonpedunculated uterine leiomyoma in puerperium. The patient was a 32-year-old woman, gravida 2, para 1, who was admitted to our department from a private maternity clinic with a considerable drop in haemoglobin 23 hours after delivery of a healthy boy. The placenta had easily and spontaneously delivered. On admission to our department her haemoglobin was 6.3 g/dl. Pelvic examination disclosed the presence of fresh blood clots in the vaginal vault. A circular firm structure, 12 by 12 cm, was noted within the external cervical os. This mass was immovable. Total abdominal hysterectomy without salpingo-oophorectomy was immediately performed and the patient's postoperative course was uneventful. In conclusion, in this patient the uterine leiomyoma obstructed the cervical os and prevented the passage of lochia resulting in haematometra, uterine atony and subsequent serious uterine haemorrhage. In such cases ostetricians and gynaecologists should proceed immediately with surgical intervention to avoid a life-threatening situation.

Immunohistochemical evaluation of cathepsin D in normal, hyperplastic and malignant endometrium: correlation with hormone receptor status c-erbB-2, p53, Rb proteins and proliferation associated indices.

The immunohistochemical expression of cathepsin D was performed in paraffin embedded tissue from 79 endometrial carcinomas, 35 cases of hyperplasia, and 32 normal endometrium using the streptavidin-biotin method to investigate the role of cathepsin D (CD) in these lesions and its possible relationship with other potential and established prognostic markers. The association between CD and the other markers was assessed by univariate analysis. Tumor cell CD expression was lower in the group of carcinomas compared to the normal proliferative (P = 0.022) and secretory endometrium (P = 0.0005). In addition, hyperplastic cell CD expression was lower compared with epithelial cell CD expression in the secretory phase of normal endometrium (P = 0.009). Malignant cell CD expression was inversely correlated with tumor stromal cells (P = 0.007). A positive relationship of stromal cell CD expression with pRb (P = 0.046) and PCNA score (P < 0.0001) was detected in the group of carcinomas. In the proliferative phase of normal endometrium, epithelial CD expression was positively correlated with estrogen status (P = 0.015). The data show that down-regulation of CD expression is an early event in endometrial carcinogenesis. In addition, stromal cell CD expression may be involved in cell growth process in endometrial carcinomas.

Immunohistochemical expression of Retinoblastoma gene product in normal, hyperplastic and malignant endometrium. Correlation with p53 protein expression, c-erbB-2, hormone receptors' status and proliferative activity.

Alterations of the retinoblastoma (Rb) gene have been described in several human neoplasms and recently, it has been suggested that these alterations may play a role in the development of endometrial carcinomas. Paraffin sections from 31 cases of normal endometrium (16 proliferative, 15 secretory), 35 hyperplastic lesions and 89 endometrial carcinomas were investigated immunohistochemically for Rb protein (pRb) expression. The results were compared with p53 and c-erbB-2 protein expression, estrogen (ER) and progesterone (PR) receptors' status and with clinicopathological prognostic factors. pRb was expressed in normal, hyperplastic and neoplastic epithelium. Proliferative endometrium showed more intense and extensive pRb staining than secretory endometrium. pRb reactivity was heterogeneous in the hyperplastic endometrial cells. Lack or focal (< 10% of endometrial cells) pRb immunostaining was noted in 56.2% and 27% of carcinomas, respectively. In the remaining cases (16.8%) pRb staining was heterogeneous or diffuse. The absence or presence of pRb expression was independent of grade and stage. In normal proliferative and secretory endometrium, pRb expression was correlated with PR (p = 0.006 and p = 0.001, respectively), PCNA (p = 0.04 and p = 0.01, respectively) and MIB1 (p = 0.02 and p<0.0001, respectively) expression. In hyperplasias, pRb was related to PR (p = 0.016) and MIB1 (p < 0.0001) expression. In carcinomas, a relationship of pRb expression with p53 (p = 0.0015), ER (p = 0.0002), PR (p = 0.0004) and PCNA (p = 0.013) status was detected. We suggest that the absence or presence of pRb expression does not seem to be associated with the progression of endometrioid carcinoma. In addition, pRb seems to be normally regulated in relation to the proliferative growth fraction of the tumours.

Appendicectomies in Albanians in Greece: outcomes in a highly mobile immigrant patient population.

BACKGROUND: Albanian immigrants in Greece comprise a highly mobile population with unknown health care profile. We aimed to assess whether these immigrants were more or less likely to undergo laparotomy for suspected appendicitis with negative findings (negative appendicectomy), by performing a controlled study with individual (1:4) matching. We used data from 6 hospitals in the Greek prefecture of Epirus that is bordering Albania. RESULTS: Among a total of 2027 non-incidental appendicectomies for suspected appendicitis performed in 1994-1999, 30 patients with Albanian names were matched (for age, sex, time of operation and hospital) to 120 patients with Greek names. The odds for a negative appendicectomy were 3.4-fold higher (95% confidence interval [CI], 1.24-9.31, p = 0.02) in Albanian immigrants than in matched Greek-name subjects. The difference was most prominent in men (odds ratio 20.0, 95% CI, 1.41-285, p = 0.02) while it was not formally significant in women (odds ratio 1.56, 95% CI, 0.44-5.48). The odds for perforation were 1.25-fold higher in Albanian-name immigrants than in Greek-name patients (95% CI 0.44- 3.57). CONCLUSIONS: Albanian immigrants in Greece are at high risk for negative appendicectomies. Socioeconomic, cultural and language parameters underlying health care inequalities in highly mobile immigrant populations need better study.

Tumor markers in stage P1 bladder cancer.

BACKGROUND: The infiltration of muscularis mucosa in superficial bladder cancer has been reported to be predictive of an unfavourable course of the disease. MATERIALS AND METHODS: We studied immunohistochemically Ki-67, PCNA and p53 tumour markers in 68 P1a and Pib bladder tumours. RESULTS: A statistically significant difference (p = 0.01) was found in the distribution of grades between stages P1a and P1b, with more grade 3 and less grade 2 tumours in the latter category. Univariate analysis revealed a strong association of Ki-67 (p = 0.001) and PCNA (p = 0.032) only with stage. P53 protein expression did not have any significant association with either stage or grade. In 60 patients entered into the multivariate analysis a clearly predominant, significant effect of stage on Ki-67 (p = 0.000) was shown. CONCLUSION: Increased proliferative activity when compared to P1a is present in P1b bladder tumours, as detected by the increased expression of Ki-67 proliferating antigen. The immunohistochemical study of Ki-67 antigen may help in predicting stage P1 tumours' behaviour, even in cases where pathological distinction of P1a and P1b substages is difficult.

Immunohistochemical localization of metallothionein in endometrial lesions.

Metallothioneins (MTs) are a group of ubiquitous low-molecular-weight proteins essential for the protection of cells against heavy metal ion toxicity. The immunohistochemical expression of MT was studied by immunohistochemistry using a monoclonal antibody (E9) against a conserved epitope of I and II isoforms in a series of 89 endometrial carcinomas, 34 cases of hyperplasia, and 32 samples of normal endometrium. In secretory phase endometrium, extensive MT expression was detected in most cases (92.4%). In contrast, MT immunoreactivity was confined to small foci in 22.2% of proliferative phase cases. The MT values in normal endometrium were inversely correlated with oestrogen receptor (ER) content (p<0.0001), progesterone receptor (PgR) content and with PCNA (p<0.0001) and MIB1 (p=0.001) scores. In hyperplastic lesions, MT expression was detected only in 3.3% of cases, while in the group of carcinomas it was observed in 23.1%. A statistically significant difference of MT expression was observed between carcinomas and simple hyperplasias (p=0.03). In carcinomas, MT expression was positively correlated with grade (p=0.0065), MIB1 (p=0.022), and p53 (p=0.006) expression, and inversely with PgR (p=0.03). A trend of inverse correlation between MT and ER receptor was also detected (p=0.07). These data suggest that MT expression seems to be under hormonal control in normal endometrium; that it may modify p53 expression; and that it could be used as an additional biological marker indicating aggressive behaviour in endometrial lesions.

Distribution of CD1a-positive Langerhans cells and lymphocyte subsets in transitional cell carcinoma of the urinary bladder. An immunohistological study on frozen sections.

The distribution of CD1a-positive Langerhans cells, CD4-positive T-helper cells, and CD8-positive T-suppressor cells in 36 patients with transitional cell carcinoma of the urinary bladder was studied immunohistochemically on frozen sections. Multiple tissue specimens from the tumour, the adjacent mucosa, and random bladder wall biopsies were examined. Langerhans cells were mainly interspersed among the tumour cells, whereas T-helper cells were present in aggregates in the stroma. T-suppressor cells were present both in aggregates in the stroma and among the tumour cells. There was a marginal relationship between the density of Langerhans cells and the density of T-helper/inducer cells and a good relationship with CD8-positive cells. There was no statistically significant difference in the population density of Langerhans cells associated with the various clinicopathological variables, including growth pattern, histological grade and stage, or patient's age and sex. On the contrary, a statistically significant difference was found in the CD1a/CD4 ratio among specimens of different grades. These results show that CD1a cell populations correlate with T-cell populations in bladder cancer, suggesting that Langerhans cells take part in the immune response carried out by T lymphocytes, their task being apparently antigen presentation.

HLA-DR antigen expression and lymphocyte subsets in transitional cell carcinoma of the urinary bladder. An immunohistological study on frozen sections.

Lymphocyte subpopulations (B cells, CD4, CD8), interleukin-20 receptors (IL-2), monocytes/macrophages (Leu M5), and HLA-DR antigen expression were studied immunohistochemically on frozen sections from 38 bladder cancer specimens. T cells predominated over B cells in all tumours. CD4-positive lymphocytes predominated over CD8 in the stroma (CD4/CD8: 1.35/l), while in epithelial tumour cells CD8 was the prominent subpopulation (CD8/CD4: 1.75/l). Aberrant HLA-DR expression was found in 21.05 per cent of bladder tumours. A strong correlation between CD4 and CD8 population densities and macrophages with the other subpopulations was noticed. In HLA-DR-positive tumours, there was no correlation of the percentage of positive cells with CD4- and CD8-positive lymphocyte populations. Various parameters including IL-2 receptors, B cells, CD8- and CD4-positive cells, and macrophages did not differ significantly between the groups of tumours expressing and not expressing HLA-DR antigen. There were no statistically significant differences in the population densities of B cells, CD8- or CD4-positive cells, IL-2 receptor, monocytes/macrophages, and HLA-DR antigen expression among various clinicopathological parameters, including growth pattern, histological grade and clinical stage or patient's age and sex. These findings suggest that in transitional cell carcinoma of the urinary bladder, HLA-DR antigen expression is independent of lymphocyte subpopulations. It is therefore possible that HLA-DR expression by tumour cells reflect the existence of separate HLA-DR-positive or HLA-DR-negative tumour clones.

Growth fractions in bladder cancer defined by Ki67: association with cancer grade, category and recurrence rate of superficial lesions.

Predicting future tumour behaviour has always been a major task when treating bladder cancer. Ki67 monoclonal antibody has been reported to be a good marker of proliferative activity in a variety of tumours. We have studied the association of growth fractions defined by the monoclonal antibody with tumour grade, category and recurrence rate of superficial lesions in 34 patients with bladder cancer and 15 normal controls. Mean Ki67 indexes (% stained cells) were 0.07 +/- 0.02% in normal urothelium, 1.27 +/- 1.55% in grade 1, 12.23 +/- 8.32% in grade 2 and 16.42 +/- 11.82% in grade 3 tumours, while the values were 5.45 +/- 5.87%, 12.66 +/- 9.81% and 17.18 +/- 12.41% in categories pTa, pT1 and T2-T3 respectively. Recurrence and non-recurrence groups of patients showed indexes of 13.29 +/- 9.49% and 4.15 +/- 5.0% respectively. Statistically significant differences in Ki67 values between normal urothelium and tumour, between tumours of different grades and categories as well as between recurrence and non-recurrence groups of patients led to the conclusion that Ki67 monoclonal antibody is a good tool in defining tumour behaviour in bladder cancer.