Adenomyolipoma of the endometrium--a hamartoma?
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Biomedical subjects
Publications and source records attributed to E Sivridis.
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The presence of the Actinomyces usually is not determined by the common histologic examination of preparations of tonsillar tissue which has been removed surgically. The Actinomyces are common saprophytic microorganisms which are found inter alia in the oral cavity and palatine tonsils. In this study, the authors examined histologically 238 surgical preparations of tonsillar tissue. In 84 of these, that is 35.21%, it has been noted, except the others, the presence of Actinomyces israeli. At the same time, the authors state their views concerning the contribution of the Actinomyces of tonsillar crypts to the pathogenesis of chronic tonsillitis.
Magnetocardiographic (MCG) patterns, produced by the electrical activity of the heart, were investigated in 38 full term pregnant women (17 pre-eclamptic and 21 with uncomplicated pregnancies), by means of a superconducting quantum interference device (SQUID). The most important difference was noted in the waveform amplitudes of the MCG recordings; these were appreciably lower in women with pre-eclampsia compared to those in the normal control series, although in both groups the emitted magnetic fields ranged at approximately the same frequency band. Electrocardiographic (ECG) QRS complexes were represented clearly only in the low MCG waveform amplitudes, and these were related to the presence of widespread obliterative endarteritis in the fetal vasculature of the placentae. The above MCG findings are consistent with an increased contractibility of the myocardium in pregnant women with hypertensive disease secondary to the increased peripheral resistance.
Nucleolar organiser regions (NORs), which are important for regulating protein synthesis, were identified in 20 breast carcinomas by means of a silver (Ag) staining technique. Infiltrating neoplasms with metastases in four or more axillary lymph nodes possessed, on average, a greater number of AgNORs per cell nucleus compared with neoplasms without nodal disease, or with one to three positive lymph nodes. The size, morphology, and distribution of AgNORs within the nucleus were also different in the two study groups. Overall, these findings suggest that breast carcinomas with multiple, irregular, and widely dispersed AgNORs tend to be of high grade malignancy.
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In a histopathological review of 171 cases of endometrial adenocarcinoma, 42 neoplasms demonstrated lymphatic and/or vascular invasion. This finding was significantly correlated with depth of myometrial involvement and stage of disease at operation. Tumour cell type, and histological grade were correlated to a much lesser extent, whilst the patient's age bore no relation. Prognosis was significantly poorer in patients whose adenocarcinomas had invaded lymphatic and/or vascular spaces compared to those whose neoplasms had not. These observations emphasize the importance of considering lymphatic/vascular invasion in staging endometrial adenocarcinomas.
An immunohistochemical technique was used to demonstrate oestrogen and progesterone binding by endometrial glandular epithelial cells at various stages of the menstrual cycle. A cross-section of steroid binding sites, including low affinity, concentration dependent Type II and III binding sites, were demonstrated but only in cells which contain the classical high affinity receptor. The technique demonstrated both free binding sites and receptor-hormone complexes within the cytoplasm but was poorly effective in demonstrating nuclear complexes. Oestrogen binding sites were shown to reach a peak during the late proliferative and early secretory phases of the cycle: oestrogen binding capacity remained high during the mid and late secretory phases. Progesterone binding capacity rose progressively throughout the proliferative and early secretory phase.
Scanty argyrophil cells are present in a substantial proportion of normal endometria, particularly during the secretory stage of the cycle. Argyrophil cells are also present in the various types of hyperplastic endometria and are found in more than half of endometrial adenocarcinomas. In some endometrial neoplasms they are present in abundance, but tumours rich in such cells do not have any features suggestive of a carcinoid tumour and are morphologically identical to adenocarcinomas of similar grade which are devoid of argyrophil cells. Endometrial adenocarcinomas containing argyrophil cells tend to be well differentiated and tend not to invade deeply into the myometrium. It is suggested that Müllerian epithelial stem cells possess a potentiality for differentiation into APUD cells.
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The prognostic and predictive role of c-erbB-2 oncoprotein in human malignancies remains controversial. The pattern of expression and the biological behaviour of c-erbB-2 protein was investigated in a series of 89 locally advanced squamous carcinomas of the head and neck. Possible associations between c-erbB-2 and T,N-stage, histological grade, microvessel density and the expression of bcl-2 and p53 proteins were sought. Biopsy material had been collected prior to the initiation of treatment which consisted of platinum based induction chemotherapy or concurrent chemotherapy and radiotherapy. In all cases, follow-up of at least 2 years duration was available. Positive staining was seen in 27 out of 89 (30.4%) cases and was invariably cytoplasmic, exhibiting strong reactivity in more than 50% of tumour cells. Such c-erbB-2 overexpressing tumours were not associated with a response to radiotherapy and/or induction chemotherapy. Further, survival analysis did not disclose any difference in the overall or relapse free survival between c-erbB-2 positive and negative cases. Similarly, no relationship was found with T,N-stage, histological grade and bcl-2 or p53 expression. There was, however, a significant inverse association between c-erbB-2 expression and microvessel density (p = 0.0001). Interestingly, tumours with low vascular grade (VG; MS < 26) and positive c-erbB-2 expression were less frequently associated with local aggressiveness compared to c-erbB-2 negative tumours and low VG (5/27 vs. 12/18; p = 0.001), or to c-erbB-2 negative tumours and high VG (MS > 27) (5/27 vs. 19/44; p = 0.03). These differences were statistically significant but were not related to treatment response or prognosis. Nonetheless, when patients with highly angiogenic tumours were analysed for survival, irrespective of the c-erbB-2 status, they showed a poorer prognosis than those having a low microvessel density (p = 0.06 and 0.05 for overall and relapse free survival, respectively). Six out of 89 patients presented with distant metastases, five of which had tumours negative for c-erbB-2 expression. Our results seem to indicate that the pattern of c-erbB-2 expression in locally advanced inoperable head and neck cancer is exclusively cytoplasmic. c-erbB-2 reactivity is of little value in predicting survival or chemo-radiotherapeutic response. Expression of genes related to angiogenesis or other invasion and migration pathways are, apparently, more important.
This study evaluated the frequency and the prognostic significance of bax, bcl-2 and p53 proteins in stage B and C adenocarcinomas of the colon and rectum. Paraffin-embedded specimens from 268 patients with colorectal adenocarcinomas, treated with surgery, were assessed; of these 160 cases were Duke's stage B and 108 cases were Duke's stage C disease. Adjuvant chemotherapy was given to all stage C and to 108 out of 160 stage B cancer patients, while those having rectal malignancy also received pelvic radiotherapy. Duke's stage B patients were treated either with surgery alone or with surgery and radiotherapy. The follow-up period at the time of analysis ranged from 12-72 months (median 32 months). Immunohistochemical expression of bax, bcl-2 and mutant p53 proteins was detected with a frequency of 42%, 37% and 48%, respectively. However, the expression was strong only in 17% of tumours, on average. A strong bcl-2 expression was significantly associated with a strong bax expression (p < 0.0001) and with absence of p53 nuclear accumulation (p < 0.005). There was, however, no correlation between bax and p53 proteins. Furthermore, bcl-2 expression was significantly more frequent in grade I and 2 adenocarcinomas compared to grade 3 disease (p = 0.01). In stage B (but not C) adenocarcinomas, bax expression was directly associated with higher risk of local relapse (p = 0.04). By contrast, cases with p53 nuclear accumulation, when they had received adjuvant radiotherapy, were significantly associated with a lower incidence of local relapse (p = 0.01), but a higher rate of distant metastasis (p = 0.06). Multivariate analysis for disease free and overall survival showed that bax expression and high Duke's stage were independent prognostic parameters associated with an unfavourable outcome (p = 0.009 and p = 0.0001, respectively). It was concluded that the immunohistochemical expression of bax is a marker of poor prognosis and of a higher risk of local relapse in patients with colorectal adenocarcinomas. p53 nuclear accumulation is associated with a better local control, following radiotherapy and with a metastatic phenotype. The development of novel monoclonal antibodies recognising specifically the mutated versus the wild type form of proteins would apparently improve the prognostic and predictive value of the immunohistochemically detected apoptotic proteins.
Ewing's sarcoma arising in the right fibula was diagnosed in a 12 years old female, considering clinical presentation, radiological findings and histological features. Our work points towards a possible neuroectodermal origin of Ewing's sarcoma, since MIC2/12E7 marker was found to be positive. Translocation t (11;22) (q24;q12) was found as the main cytogenetic change in this tumor, by means of FISH analysis.
BACKGROUND AND PURPOSE: Intra-tumoural neoangiogenesis is an essential process for tumour progression. Although intensification of angiogenic pathways during cytotoxic therapy has been reported by a few experimental studies, the role of angiogenesis in response to radiotherapy is unclear. We recently reported an adverse effect of intense angiogenesis in the radiotherapy outcome of squamous cell head and neck cancer (SCHNC). In the present study we investigated the radiotherapy-induced changes in the microvessel density (MVD) and in the expression of the angiogenic factor thymidine phosphorylase (TP) in SCHNC. PATIENTS AND METHODS: Twenty-four patients with SCHNC underwent a biopsy of the primary lesion immediately before and after delivery of 20Gy of conventionally fractionated radiotherapy. The MVD and the expression of TP was assessed with immunohistochemistry. RESULTS: The irradiated samples were composed of cancer cell islets or bands, immersed within avascular degenerated tissue. In tumours that did not reach complete response after the end of radiotherapy, these viable cancer tissue areas had a significantly higher MVD (p=0.006) and increased percentage of cancer cells with nuclear TP expression (p=0.0004) than the MVD and the TP expression noted in specimens before radiotherapy. TP expression in these islets was directly related to the MVD (p=0.004, r=0.56). CONCLUSION: The present study supports the idea that intensified angiogenic growth (angiogenic regeneration) during radiotherapy is associated with failure of radiotherapy.
Angiogenesis occurs more frequently in endometrial carcinomas developing against a background of endometrial atrophy rather than carcinomas arising from a hyperplastic endometrium. In some studies, angiogenesis is associated with unfavourable histopathological features, but not in others. In all studies, however, increased angiogenesis is related to poor prognosis. Vascular endothelial growth factor (VEGF) is the major stimulus for endothelial cell proliferation in endometrial carcinomas and is, therefore, associated with high angiogenesis. VEGF expression at the invading tumour front is 4-10 times higher than in the inner tumour areas and is significantly associated with poor prognosis, particularly within stage I endometrial disease. However, since its stimulating effect on endothelial cells is basically dependent on the presence of VEGF receptors, i.e. the flk-1(KDR), the detection of a functionally intact angiogenic pathway VEGF/flk-1 (KDR) is a more reliable and, indeed, independent prognostic parameter. The other angiogenic factor, thymidine phosphorylase (TP), is related to the adverse histopathological variables of the non endometrioid carcinomas, high tumour grade, deep myometrial invasion and advanced stage of disease, at least at the invading tumour front, and its prognostic significance is, therefore, limited. Furthermore, it is not directly related with increased angiogenesis. However, the simultaneous expression of high VEGF / high TP activity at the invading tumour front emerged as the most potent angiogenic phenotype in endometrial carcinomas, indicating that the two molecules are co-operating. Furthermore, a high TP activity in the stromal cells is associated with a high density of activated macrophages which further promotes endometrial tumour angiogenesis.
OBJECTIVE: To investigate whether anemia, a putative factor counteracting the efficacy of radiotherapy, up-regulates the endogenous markers of intratumoral hypoxia, the hypoxia inducible factors HIF1 alpha and HIF2 alpha. MATERIALS AND METHODS: Forty-two hysterectomy specimens harboring endometrial adenocarcinomas of the endometrioid cell type, stage I were investigated immunohistochemically for the expression of HIF1 alpha, HIF2 alpha and the down-stream inducible expression of vascular endothelial growth factor VEGF. The results were correlated with hemoglobin (Hb) levels. RESULTS: There was no significant association between Hb levels and the expression of HIF1 alpha, HIF2 alpha or VEGF in our material. CONCLUSION: Activation of hypoxia pathways is an intrinsic self-regulated process, independent of Hb levels in endometrial adenocarcinomas. Other factors such as microvessel density (MVD), vessel/tumor cell distance or genetic events may be important.
The role of p53 and bcl-2 apoptosis related proteins in the pathogenesis of endometrial cancer remains unclear. We immunohistochemically examined 133 surgically removed tumour specimens from patients with stage I endometrial cancer for p53 oncoprotein nuclear expression and bcl-2 cytoplasmic reactivity. 114/133 (86%) cases were of the endometrioid histological sub-type. A cut-off point of 10% of cells with strong reactivity was used for positivity. Positive p53 expression was observed in 12/133 (9%) and positive bcl-2 in 40/133 (30%) cases. p53 expression was not related to bcl-2 expression. No association of p53 and bcl-2 with depth of myometrial invasion, vascular invasion or histological grade was observed. However, continuous variable analysis revealed a trend of low grade cases to have a higher percentage of bcl-2 positive cells (16.3 + 27% vs. 7.8 + 16%; p = 0.09, unpaired two tailed t-test). Interestingly, a statistically significant association of p53 positivity with age was also observed (p = 0.03). A strong association of high grade with depth of myometrial invasion (p = 0.006) and vascular invasion (p = 0.0001) was also noticed. In addition, the presence of adenomyosis was also associated with low grade (p = 0.01) and absence of vascular invasion (p = 0.02). We conclude that although loss of bcl-2 protein expression and p53 mutant protein nuclear accumulation are early events in the endometrial cancer progression, histological grade and vascular invasion remain the most important factors defining local invasive behaviour of endometrial cancer.