Vascular endothelial growth factor (VEGF) expression and microvascular density in salivary gland tumours.

This study investigates whether salivary tumours with different morphology and evolution also differ in terms of neovascularization and VEGF expression and the prognostic value of the results. Surgical specimens from 45 patients - 8 pleomorphic adenomas (PA), 7 Warthin tumours (WT), 5 basal cell adenomas (BA), 6 carcinomas ex-pleomorphic adenoma (CEPA), 6 mucoepidermoid carcinomas (MEC), 5 acinic cell carcinomas (AC), 4 adenoid cystic carcinomas (ACC) and 4 adenocarcinomas not otherwise specified (ADK NOS) - were immunostained. In malignant salivary tumours, the following mean microvascular density (MVD) values were recorded (± SD = Standard Deviation): 27.61 (SD ± 2.27) in cases with CEPA, 27.08 (DS ± 7.81) in AC and 32.93 (SD ± 7.76) in ADK NOS, with lower values for MEC 24.31(SD ± 2.88) and for ACC 22.13 (SD ± 5.44). For benign tumours, an MVD of 35.71 (SD ± 2.09) was recorded in WT and lower average values in PA (MVD = 14.84; SD ± 4.86) and in BA (MVD = 23.96; SD ± 9.13). MVD did not correlate with the investigated clinicopathological parameters. The VEGF expression is significantly more important (p = 0.001) in malignant salivary tumours as compared with benign ones. The VEGF expression and the microvascularization in salivary gland tumours are important elements to be considered when formulating a diagnosis and assessing case evolutions in patients with such tumours.

What is the significance of HLA-DR antigen expression in the extraglomerular mesangium in glomerulonephritis?

INTRODUCTION AND AIMS: The HLA-DR antigen is a HLA class II molecule involved in the presentation of antigenic peptides to the T cell receptor, thus regulating the immune response. Renal expression of the HLA-DR antigen may indicate specific sites of immunologically-mediated kidney injury in glomerulonephritis (GN). The aim of our study was to assess the presence of the HLA-DR antigen along the nephron including the extraglomerular mesangium in GN. METHODS: A cross-sectional study of 22 patients with glomerulonephritis, mean age: 46.59±10.77 years, 14 male and 8 female, was conducted. Conventional stains, as well as immunohistochemistry for the HLA-DR Antigen Alpha-Chain were employed on kidney biopsies. Immunohistochemistry was assessed using a semi-quantitative score: 0-absent, 1-mild, 2-moderate, 3-intense. Statistical analysis was performed using SPSS17. RESULTS: Four patients presented Focal and Segmental Glomerulosclerosis (FSGS), 5 patients: membranoproliferative GN, 7 patients: membranous nephropathy, 3 patients: mesangial proliferative GN, 2 patients: minimal change disease (MCD), and 1 patient: crescentic GN. Regarding the percentage of cases with HLA-DR positive cells along the nephron out of 22 patients: glomerular endothelial cells were 100% positive, intraglomerular mesangium cells were 81.8% positive, podocytes were 36.4% positive, extraglomerular mesangium cells were 31.8% positive, proximal tubule cells were 95.5% positive, distal tubule cells were 68.2% positive, interstitial capillaries were 77.3% positive, and cells of interstitial infiltrates were 27.3% positive. The percentage of cases staining positively for the HLA-DR antigen in the extraglomerular mesangium was 25% in FSGS, 60% in membranoproliferative GN, 0% in membranous nephropathy, 33.3% in mesangial proliferative GN, 100% in minimal change disease and 0% in crescentic GN. CONCLUSIONS: A prominent HLA-DR antigen distribution was found on glomerular endothelial cells, intraglomerular mesangium cells and proximal and distal tubular cells. Extraglomerular mesangium cells and podocytes stained variably for the HLA-DR antigen, as did the cells of the interstitial infiltrates. The extraglomerular mesangium which serves as a portal of entry into the intraglomerular mesangium is endowed with antigen-presenting capabilities and is a region where induction of immune reactions could take place.

Molecular characterization of apoptosis by the immunohistochemical evaluation of Bcl-2 in breast cancer.

PURPOSE: Immunohistochemical markers are used to classify breast cancer into molecular subtypes biologically and behavior distinct. The Bcl-2 gene has been implicated in a number of cancers and it is also thought to be involved in resistance to conventional cancer treatment. The aim of this study was to investigate apoptosis in breast cancer cells and in molecular groups using IHC expression of Bcl-2. MATERIALS AND METHODS: Our study included 61 patients that been followed up five years since diagnosis. The traditional prognostic factors: age, tumor size, histological type, histological grade, clinical stage and the status of the lymph nodes were used for primary morphological evaluation. Molecular classification of cases and Bcl-2 assessment was performed by immunohistochemistry in agreement with data from the literature. RESULTS: More than an half of tumors were positive for Bcl-2 showing a favorable response to endocrine therapy. The average age of the patients, hormonal status, tumoral diameter and histological grade showed significant differences statistically. Most of positive cases for Bcl-2 belong to the luminal tumor group, while non-luminal tumors have a negative reaction. When we compared well-known histological types, we noticed insignificant issues regarding score groups for Bcl-2; in exchange, when they were compared into molecular groups, we obtained the strongest statistical correlation. CONCLUSIONS: Assessment of apoptosis by Bcl-2 leads to the identification of molecular groups with different immunohistochemical and clinical features and different survival rates, better for Bcl-2 positive tumors and worse in Bcl-2 negative tumors.

CD34+ fibroblast-like cells in the interstitial infiltrates in glomerulonephritis - an immunohistochemical observation.

CD34 cells in the interstitial infiltrates in glomerulonephritis (GN) could be the turning point between regenerative processes and interstitial fibrosis. The aim of our study was to assess the presence of CD34+ cells in the interstitial infiltrates in GN. A cross-sectional study of 33 patients with glomerulonephritis, mean age: 43.3 ±11.31 years, 20 male and 13 female, was conducted. Conventional stains, as well as immunohistochemistry for the CD34 antigen were employed on kidney biopsies. Strength of immunohistochemical reaction was assessed semi-quantitatively. Regarding the percentage of cases with CD34+ cells in the interstitial infiltrates out of 33 patients: cells of interstitial infiltrates were 27.3% positive. The percentage of cases showing CD34+ cells at the level of interstitial infiltrates was: 44.4% in FSGS, 14.3% in membranoproliferative GN, 28.6% in membranous nephropathy, 20% in mesangial proliferative GN, 0% in minimal change disease, and 50% in crescentic GN. With the exception of minimal change disease, CD34+ cells were found in the interstitial infiltrates in all histopathological forms of GN. Some of these cells were spindle-shaped fibroblast-like cells. As inflammation in the tubulointerstitial compartment either resolves or proceeds to fibrosis, aims at reversing this process will benefit from analyses of the interstitial infiltrates harboring CD34+ cells.

Pseudobenign prostate carcinomas: causes of false-negative biopsy results.

Prostate carcinomas are continuously surprising the pathologists through their multitude of variants and histological subtypes, some of them being recently described and characterized. Among these are individualized: atrophic carcinoma, foamy gland, pseudohyperplastic, microcystic, certain subtypes of ductal adenocarcinoma and hormone-treated adenocarcinoma, which because of minimal architectural and/or cytological atypia are often under-diagnosed, especially in small tissue fragments. This paper presents the morphological criteria, including information provided by some immunohistochemical markers for positive and differential diagnosis of these variants/subtypes of prostate adenocarcinoma with which the pathologist should be familiar and avoid their confusion with a series of similar histological structures or benign/premalignant lesions.

Evaluation of proliferation potential in thyroid normo-/hypofunctioning and hyperfunctioning nodules.

INTRODUCTION: Thyroid follicular adenomas (FA) and adenomatous thyroid nodules (AN) - lesions that are frequently found in areas with iodine deficiency, can be normo-/hypofunctioning (scintigraphically cold - SCN) or hyperfunctioning (scintigraphically hot - SHN) nodules. AIM: Evaluation of proliferation potential in thyroid nodules on tissue samples obtained at surgery from euthyroid patients clinically diagnosed with SCN and from patients with thyroid hyperfunction and SHN. MATERIALS AND METHODS: We investigated the proliferation activity estimated by assessing PCNA and Ki-67 proliferation markers in 20 SCN (eight FA and 12 AN) and 16 toxic nodules (six hyperfunctioning FA and 10 toxic multinodular goiters), on formalin-fixed and paraffin-embedded tissue samples, 4-5 µm thick; we used the immunohistochemical technique in LSAB system (DAB visualization) with anti-PCNA (PC10) and anti-Ki-67 (MIB-1) monoclonal antibodies. For each case, we calculated the proliferation index PI-PCNA and PI-Ki-67. The dates were statistically evaluated using the t-unpaired test. RESULTS: We observed a higher PI-PCNA in thyroid nodules than in the normal surrounding thyroid tissue, with statistically significant values for FA (14.3% vs. 3.8%; p<0.029) and also for AN (8.36% vs. 1.24%; p<0.001). The mean PI-Ki-67 in nodules vs. surrounding thyroid tissue was 1.64% vs. 1.10% in FA (p<0.35) and 1.07% vs. 0.51% in AN (p>0.05). We also noted: (1) significantly higher PI-PCNA values (p < 0.01) in FA (14.03%) than in AN (8.36%), as compared to statistically insignificant values for Ki-67 (1.64% vs. 1.07%; p>0.05); (2) increased proliferation rate (p<0.01) in thyroid nodules with aspects of lymphocytic thyroiditis (LT) (PI-Ki-67 was 1.21%) as compared to nodules without LT (PI-Ki-67 was 0.12%); (3) a mean PI-PCNA of 8.5% and PI-Ki-67 of 4.61% in toxic thyroid nodules (TTN) vs. 3.01% and 1.5% in normal surrounding thyroid, respectively. CONCLUSIONS: The clinical expression of SCN is the consequence of increased thyrocyte proliferation in the nodules; the increased proliferative potential of TTN thyrocytes is a common feature of nodules, independent of their histopathological characteristics.

B-cell transcription factors Pax-5, Oct-2, BOB.1, Bcl-6, and MUM1 are useful markers for the diagnosis of nodular lymphocyte predominant Hodgkin lymphoma.

In some instances, the overlap in morphologic features and antigen expression between nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) and classical Hodgkin lymphoma (cHL) can cause confusion in the diagnosis. In these cases, the transcription factors (TFs) B-cell specific activator protein (BSAP)/Pax-5, octamer binding protein-2 (Oct-2), B-lymphocyte-specific co-activator BOB.1/OBF.1, Bcl-6 protein and multiple myeloma-1/interferon regulatory factor-4 (MUM1/IRF-4) may aid in clarifying the diagnosis. Twenty-two cases of NLPHL were studied for the immunohistochemical expression of Pax-5, Oct-2, BOB.1, Bcl-6 protein and MUM1/IRF-4. Our results sustain the usefulness of the selected set of TFs to diagnose and distinguish NLPHL from cHL since Pax-5, Oct-2, BOB.1 and Bcl-6 are consistently expressed by lymphocyte predominant (LP) cells and reported by others to be often unexpressed in Hodgkin and Reed-Sternberg cells. By contrast, MUM1/IRF-4 protein scored negative in the majority of LP cells, but is reported to be expressed in almost all cases of cHL. Thus, although the expression of transcription factors is very heterogeneous, their simultaneous implementation for positive and differential diagnosis may be useful.

Ki-67 expression in gastric cancer. Results from a prospective study with long-term follow-up.

BACKGROUND: The characteristics of the cellular kinetic reflect the aggressiveness of the tumors and even their prognosis, many studies proving the correlation between the increased proliferation activity and a poor prognosis in a variety of neoplasms. AIM: The analysis of immunohistochemical expression of the Ki-67 antigen using the monoclonal antibody MIB1 in 61 patients with gastric cancer, the correlation with clinicopathological factors and the prognosis of the patients. MATERIAL AND METHODS: We used the primary MIB1 antibody pre-diluted, using the LSAB technique, DAB visualization. The quantification of the reaction was performed by appreciating the marking index Ki-67 (MI Ki-67). Although all the lesions were positive, we noticed a marked intratumoral heterogeneity regarding the distribution of the Ki-67 score. The tumor cells were considered Ki-67 positive in the presence of brown nuclear staining of granular or diffuse type. The tumor invasion front has shown the most numerous Ki-67 positive cells. RESULTS: In the gastric carcinomas, we remarked various Ki-67 scores. For a proper grouping of the results, we classified gastric carcinomas into two categories: carcinomas with high MI Ki-67 (≥45%) and carcinomas with low MI Ki-67 (≤45%). We noticed an increased frequency of high MI Ki-67 carcinomas in elderly patients (p=0.03) and also in the tumors developed at cardia level and those extended in the entire stomach in the moment of diagnosis (p<0.001). The histological forms associated to high Ki-67 values are represented by the anaplastic carcinoma (100% of cases) and papillary adenocarcinoma (60% of cases).We observed a close correlation between the degree of tumor differentiation and the Ki-67 score (p<0.001). The results of our study do not reveal any correlation between the Lauren's Classification of gastric carcinomas, the lymphovascular invasion, the depth of tumor invasion, the TNM stage and the Ki-67 score (p>0.05). CONCLUSIONS: In our study, immunohistochemical assessment of the tumor proliferation does not represent a prognostic factor, but seems to be useful in identifying of a group of patients with aggressive tumors, needing adjuvant postoperatory chemotherapy.

Expression of vascular endothelial growth factor (VEGF) and assessment of microvascular density with CD34 as prognostic markers for endometrial carcinoma.

INTRODUCTION: Angiogenesis plays an important role in the uncontrolled proliferation, invasion and metastasis of cancers. Increased microvessel density (MVD) is known to be associated with evolution and aggressiveness of the endometrial carcinoma (EC). The formation of new vessels depends on interactions between various hormones and growth factors. VEGF is one of the most known promoters of angiogenesis. MATERIAL AND METHODS: In this study, we intend to evaluate the relation between MVD, the VEGF expression, and the clinicopathologic factors in patients with endometrial carcinoma. Formalin-fixed, paraffin-embedded tissue from 54 patients with EC were included. MVD was assessed with anti-CD34 in most intense areas of neovascularization. A semiquantitative scoring system was used to asses the intensity and degree of staining of VEGF. RESULTS: MVD counts of patients with G1 EC was lower than patients with G2 and G3 EC. MVD counts of patients with stage I EC was lower as compared with stage II + III patients. There was no statistically significant difference between MVD counts in lymph node-negative and positive EC patients. The positive immunoreactions for VEGF were significantly more frequent in G1 EC in comparison to the patients with G2 + G3 EC. CONCLUSIONS: MVD and VEGF are important indicators of a poor prognosis in patients with endometrial carcinoma.

Prostate lesions with cribriform / pseudocribriform pattern.

Prostate lesions with cribriform / pseudocribriform architecture range from normal histological structures to infiltrative carcinoma. In each group of lesions with cribriform architecture (benign, premalignant and malignant intraductal or infiltrating), there are situations in which histological classification of the lesion is difficult or impossible on routine stains. A more wide-scale application of the immunohistochemical investigation for clearing up the problematic prostate lesions led to the definition and reclassification of cribriform lesions in distinct categories and sometimes very different in terms of progression, prognosis and treatment. This paper proposes an overview of the prostate lesions with cribriform / pseudocribriform architecture, emphasizing the morpho-immunohistochemical criteria for positive and differential diagnosis.

Prostatic blue nevus.

We report the case of a 69-year-old patient with no significant personal urological history. The clinical and ultrasound examination revealed a prostatic gland with increased volume and homogenous appearance. After transurethral resection, multiples gray-brown-blackish prostatic chips were obtained, which could be confused with a malignant melanoma. The histological routine examination in conjunction with the histochemical (Fontana-Masson) and immunohistochemical (S100, HMB45) reactions established the diagnosis of prostatic blue nevus. The presence of melanin in prostatic tissue is an unusual aspect, being encountered three distinct lesions: blue nevus, melanosis and malignant melanoma. Recognition and correct classification of each of these three entities is fundamental, concerning the clinical and prognosis implications.

The immunohistochemical expression of the p53-protein in gastric carcinomas. Correlation with clinicopathological factors and survival of patients.

BACKGROUND: P53-tumor suppressor gene has an essential role in controlling cell cycle and initiating carcinogenesis. In the case of gastric cancer, the role of p53-protein accumulation as prognostic factor is controversy. Various results are due to the different methods of study regarding patients' selection, immunohistochemical techniques used and the quantifying systems for immunoreactions. AIM: Assessment of p53-immunohistochemical expression in 61 patients with gastric carcinomas and the correlation with clinicopathological factors (gender, age, location, macroscopic, and histological type, degree of tumor differentiation and TNM-stage) and patients' survival. MATERIAL AND METHODS: From the total number of 265 patients (186 males and 79 females) diagnosed with gastric cancer in the period 1998-2002, 61 operated patients were selected. On this group, we performed a prospective study regarding the evolution and aggressiveness of gastric cancer, on a duration of five years. Survival time was calculated from the month of the surgical intervention until the month of death or confirmation of survival, and survival rate was represented by the percentage of survivals at the end of the observed interval (in years and months). We used the monoclonal antibody DO7 that detects the wild and mutant form of p53-protein, by EnVision technique and DAB-visualization. We considered positive reaction only in the presence of brown staining of the nuclei. RESULTS: P53-immunoreactions were positive in 25 gastric cancers (41%). We obtained positive stainings in 41.9% cases in men and 38.9% women. We found positive p53-immunoreactions in all the carcinomas developed in the upper third of the stomach (100%), in 53.3% of the corporeal tumors, 50% of the pangastric tumors; according to Lauren's classification, we noticed a significantly increased immunoreaction of p53 in the intestinal-type carcinomas. Among histological types, papillary, mucinous, anaplastic and tubular adenocarcinomas presented a relatively increased percentage of p53-positive immunoreactions. P53-positive stainings are more frequently encountered in moderate/poor differentiated carcinomas and those associated with lymphovascular invasion; according to pT- and pN-stage, we remarked a significantly increase of the number of p53-positive cases (p=0.02291 and p=0.038264). Five-year survival rate for patients with p53-positive carcinomas was significantly lower in comparison to the patients p53-negative (8% vs. 22.2%, p=0.0326). CONCLUSIONS: Immunohistochemical evaluation of p53-protein represents in our study an important prognostic factor, allowing the selection of a group of patients with an aggressive therapeutic indication, such as extensive lymphadenectomy and adjuvant chemotherapy.

Amplification of HER-2 gene in breast cancer: immunohistochemical and FISH assessment.

The invasive mammary cancer is the most frequent malignant tumor of women. Different inherited or acquired molecular genetic alterations have been identified in human breast cancers. A fraction of these cancers, as part of their development, undergoes gene amplification. Among the potential prognostic factors are included the biomarkers which measure or are associated with biological processes involved in tumor progression. Evaluation of HER-2 status is important in the management of patients with breast carcinoma, especially for the identification of those who are eligible for immunotherapy. The aim of our study was to evaluate HER-2 amplification status of human breast cancers by FISH and immunohistochemistry. From the total of 50 tumors included in the study, 17 (34%) presented different degrees of positivity; 33 (66%) did not express the oncoprotein HER-2. HER-2 gene and chromosome 17 status were tested in HER-2 2+ cases using FISH technique. FISH analysis may be useful to better evaluate HER-2 status in breast cancer in uncertain cases, where the immunohistochemistry score is 2+. HER-2 testing results have an important role in the clinical management of breast cancer patients. The identification of HER-2 positive tumors is certainly crucial in order to identify patient candidates for anti-HER-2 therapies.

Clinicopathologic features and five years survival analysis in molecular subtypes of breast cancer.

PURPOSE: In the last years, the incidence of breast cancer has been increasing; characteristic patterns of gene expression have emerged, reflecting molecular differences between previously known as well as newly defined subtypes of breast cancer. This study aimed to classify the molecular subtypes of breast cancers based on the expression profile of immunohistochemical markers and to evaluate their association with clinicopathological features. MATERIAL AND METHODS: A total of 173 cases of breast carcinoma were examined retrospectively using immunostains for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2). Because the triple-negative phenotype, when defined by IHC using only these three markers, is not the optimal method for defining basal-like breast cancer, we need to use an additional marker--CK 5/6. RESULTS: The luminal type was the most common subtype in breast cancer (71.6%), which was followed by the basal subtype (21.9%). HER2 subtype were 2.8% from the total of cases, being associated with the highest rate of high-graded cases. Basal type is presented largely in premenopausal women and displayed aggressive features, such as large tumor size and poorly differentiated cancers. Luminal A included the highest percentage of patients older than 60 years, the highest proportion of stage I-II tumors and well/moderately differentiated lesions. HER2-type was more frequent in premenopausal women and showed a high percentage of positive lymph nodes. CONCLUSIONS: These molecular differences have been shown to correlate very well with clinical features and survival, or even better than traditional histopathological parameters. The discovery of certain molecular characteristics of breast cancers has helped us to understand better the pathophysiology of disease and to develop more direct therapeutic strategies.

Primary malignant non-Hodgkin's lymphomas of salivary glands.

We evaluated the medical record of patients with salivary gland neoplasms diagnosed at Timisoara City Hospital from 2002 to 2009. A study has been carried out for seven years on 204 cases of salivary gland tumors and only two cases of salivary gland lymphomas were diagnosed. The two cases were females of 71- and 49-year-old, respectively. The formalin-fixed paraffin-embedded tissue samples were cut in 4 mum thick sections and stained with Hematoxylin and Eosin. The primary monoclonal antibodies for the immunohistochemical analysis were the followings: LCA (2B11, Dako), CD20 (L26, Dako), cytokeratin (MNF116, Dako), p53 (DQ-7, Dako), and PCNA (PC-10, Dako). The histopathology and immunohistochemistry suggested in the first case a low-grade diffuse large B-cell mucosa associated lymphoid tissue lymphoma and in the second case a high-grade extranodal marginal zone B-cell lymphoma.

A nodular hyperplasia of the thymic epithelium (so-called microscopic thymoma).

We investigate a case of nodular hyperplasia of the thymic epithelium which was incidentally, microscopically discovered. Macroscopically there was no sign of tumor and the thymus was surgically removed for the therapy of the clinical symptoms of the myasthenia gravis worsened in two years of evolution. Histological in a general appearance of an involuted thymic tissue, a small nodular epithelial proliferation was identified. The epithelial proliferation was classified as A-type in the WHO histological classification of the thymic epithelial tumors. Generally, these microscopic thymomas range from 0.2 mm to 0.4 mm in size that corresponds to our finding that measured 0.25/0.35 mm. This lesion was singular; on additional sections examined, we did not find other areas. Even so, there is a tight connection between the myasthenia gravis, thymomas and these microscopic thymomas, the development of a thymoma from this lesion has not been proven.

Gastric cancer: correlation between clinicopathological factors and survival of patients (III).

PURPOSE: The purpose of this study was to identify the clinicopathological factors that influence the prognosis of patients having undergone surgery for gastric cancer. The analysis of the potential prognosis factors has included in this study parameters concerning the patient (sex, age), as well as parameters related with the tumor (histological type according to the WHO classification; degree of tumor differentiation; tumor location; stage of disease; pT and pM parameters according to the TNM classification of AJCC/UICC). MATERIAL AND METHODS: From the total number of 265 patients (186 men and 79 women) diagnosed with gastric cancer in the period 1998-2002, 61 operated patients were selected. On this group, we performed a prospective study regarding the evolution and aggressiveness of gastric cancer, on a duration of 5 years. Survival time was calculated from the month of the surgical intervention until the month of death or confirmation of survival, and survival rate was represented by the percentage of survivals at the end of the observed interval (in years and months). RESULTS: The studied group consisted of 61 patients (43 men and 18 women), with ages between 30 and 80 (average age = 59.34 years). According to the maximum level of tumor invasion we identified: pTis - one case (1.6%); pT1 - four cases (6.6%); pT2 - nine cases (14.7%); pT3 - 17 cases (27.9%); most gastric cancers were included in the pT4 category (49.2%). We identified 43 gastric carcinomas with metastases in regional lymph nodes (70.5% of the cases). According to the number of lymph nodes involved: pN0 - 18 cases (29.5%); pN1 - 16 cases (26.2%); pN2 - 23 cases (37.7%); pN3 - four cases (6.6%). Distance synchronous metastases were present in 14 gastric carcinomas (pM1 - 23% of the cases), nine cases with hepatic metastases and five cases with distance peritoneal disseminations. Classification of gastric carcinomas: we identified one single case listed in the 0 stage, three cases in the IA stage, five cases in the IB stage, seven cases in the II stage, 11 cases in the IIIA stage, eight cases in the IIIB stage, and 26 cases in the IV stage. From the total of carcinomas, stage IV consisted of the greatest number of tumors, representing 42.6%. We generally remarked the increase of the number of cases in advanced stages. CONCLUSIONS: In the studied group, we noted a great number of gastric carcinomas diagnosed in stages T3 and T4 (77.1% of cases). Cardial tumor locations and gastric stump locations, as well as "signet-ring" cell and undifferentiated carcinomas prove to be aggressive, being diagnosed in advanced stages. 70.5% of gastric neoplasms presented lymph node metastases, most cases representing pN2 tumors (37.7%). 23% of neoplasms studied presented distance metastases at the time of diagnosis. We noted a significant correlation between the degree of tumor differentiation and the level of invasion, as well as the presence of distance and lymph node metastases. Survival at 5 years of patients included in the study was correlated significantly with the level of tumor invasion, the presence of lymph node and distance metastases, and the TNM stage.

Gastric cancer: correlation between clinicopathological factors and survival of patients. II.

PURPOSE: The purpose of this study was to identify the clinicopathological factors that influence the prognosis of patients having undergone surgery for gastric cancer. The analysis of the potential prognosis factors has included in this study parameters concerning the patient (sex, age), as well as parameters related with the tumor (macroscopic aspect of the tumor according to the Borrman's classification, histological type according to the WHO and Lauren's classifications, degree of tumor differentiation, tumor location, stage of disease, pT and pM parameters according to the TNM classification of AJCC/UICC). MATERIAL AND METHODS: From the total number of 265 patients (186 men and 79 women) diagnosed with gastric cancer in the period 1998-2002, 61 operated patients were selected. On this group, we performed a prospective study regarding the evolution and aggressiveness of gastric cancer, on a duration of 5 years. Survival time was calculated from the month of the surgical intervention until the month of death or confirmation of survival, and survival rate was represented by the percentage of survivals at the end of the observed interval (in years and months). RESULTS: The studied group consisted of 61 patients (43 men and 18 women), with ages between 30 and 80 (average age = 59.34 years). We have identified five papillary adenocarcinomas (8.2%), 28 tubular adenocarcinomas (46%), 17 "signet-ring" cell carcinomas (27.8%), eight mucinous adenocarcinomas (13.1%), and three undifferentiated or anaplastic carcinomas. Most gastric carcinomas examined were included in the category of poorly differentiated carcinomas (63.9%). According to the Lauren's classification, we have identified 38 intestinal type gastric carcinomas (62.3%), 17 diffuse type carcinomas (27.9%), and six mixed carcinomas (9.8%). We have identified aspects of lymphovascular invasion in 38 cases (62.3%). CONCLUSIONS: "Signet-ring" cells carcinomas, and the anaplastic ones, prove in our study to be extremely aggressive histological forms, characterized through low rates of survival. We remarked a significant correlation between the degree of tumor differentiation and survival of patients, the values recorded being significantly lower in medium and poorly differentiated carcinomas (p = 0.00871194 FS). Average survival, calculated in months, is significantly lower in patients with diffuse type carcinomas (11.3 months), in comparison with patients presenting intestinal type carcinomas (20.4 months) (p = 0.0415 S). There is a direct proportional relationship between the lymphovascular invasion and the number of positive lymph nodes. Survival after 5 years decreases significantly in the presence of lymphovascular invasion.

Warthin tumor: a curious entity--case reports and review of literature.

Warthin tumor was first described in the American literature, by Aldred Warthin, in 1929, the pathologist who named this tumor papillary cystadenoma lymphomatosum, but since than it was also knew as adenolymphoma, cystadenolymphoma, and Warthin tumor. Because of its microscopically appearance and unknown origin, this tumor entity is still fascinating head and neck surgeons and pathologist. We evaluate the histopathological aspect of Warthin tumors using Hematoxylin-Eosin stain, and immunohistochemical and histological techniques. We reviewed the medical record of patients with salivary gland tumors diagnosed at County Hospital of Timisoara from 2002-2008. In six years, 22 cases with Warthin tumor were diagnosed and among them 17 men and five women, with average age 58.47. The analysis showed that 77.27% of Warthin tumors occurred in men, and the main histopathological aspect was with 50% epithelial component. The stromal component showed a prominent B-cell population by staining with CD20, and histological techniques for mucin were positive, and reticulin fibers were revealed while using Gordon-Sweets stain. The standard and the histological and immunohistochemical techniques highlighted the complex and variable microscopical appearance of Warthin tumor that the pathologist should consider when a diagnosis for this tumor is to be considered.

The immunohistochemical expression of E-cadherin in gastric cancer; correlations with clinicopathological factors and patients' survival.

BACKGROUND: The aim of our study is to investigate the immunohistochemical expression of E-cadherin in gastric carcinomas and in surrounding mucosa (normal or with lesions of chronic atrophic gastritis, intestinal metaplasia or dysplasia). MATERIAL AND METHODS: We included 61 patients with gastric cancers operated in Emergency County Hospital Timisoara. We analyzed the E-cadherin immunohistochemical expression, the correlation with clinical and pathological factors and the outcome of the patients. The positive homogeneous pattern of staining for the cellular membranes is considered normal. The negative homogeneous or the heterogeneous pattern (of the cytoplasm and membrane) represented aberrant E-cadherin expression. RESULTS: Areas of chronic atrophic gastritis and intestinal metaplasia presented a normal pattern of immunostaining for the membranes. Aberrant E-cadherin expression was noticed in 30 cases of gastric carcinomas (49.2%) and in 11 cases (35.5%) of epithelial dysplasia in the surrounding tissue. Our results showed no correlation between E-cadherin expression and gender, age, tumor location, pT, pN, pTNM and lympho-vascular invasion. Aberrant E-cadherin immunostainings were significantly more frequent in diffuse-type carcinomas in comparison with the intestinal-type carcinomas (82.4% vs. 31.6%) (p = 0.000491 ES). Signet-ring carcinomas and anaplastic carcinomas presented a high-proportion of aberrant immunostainings (82.4% and 100%), as well as poor differentiated carcinomas (61.5%). Carcinomas with distant metastasis presented significantly more aberrant immunostainings than those without metastasis (71.4% vs. 42.6%). Five-year survival rate was significantly lower in patients with aberrant E-cadherin expression in comparison with the patients presenting normal staining (10% vs. 22.6%). CONCLUSIONS: In gastric carcinomas and areas of epithelial dysplasia, aberrant E-cadherin expression was significantly more frequent in comparison with the surrounding normal mucosa (p<0.001 ES). Our data suggest a strong correlation between Lauren's classification of gastric carcinomas and E-cadherin immunohistochemical expression. Assessment of the survival curve of the patients highlighted the role of prognostic factor for the aberrant immunohistochemical E-cadherin expression.