Assessing the performance of four different categories of histological criteria in brain tumours grading by means of a computer-aided diagnosis image analysis system.

Brain tumours are considered one of the most lethal and difficult to treat forms of cancer, with unknown aetiology and lack of any realistic screening. In this study, we examine, whether the combination of descriptive criteria, used by expert histopathologists in assessing histologic tissue samples, and quantitative image analysis features may improve the diagnostic accuracy of brain tumour grading. Data comprised 61 cases of brain cancers (astrocytomas, oligodendrogliomas, meningiomas) collected from the archives of the University Hospital of Patras, Greece. Incorporating physician's descriptive criteria and image analysis's quantitative features into a discriminant function, a computer-aided diagnosis system was designed for discriminating low-grade from high-grade brain tumours. Physician's descriptive features, when solely used in the system, proved of high discrimination accuracy (93.4%). When verbal descriptive features were combined with quantitative image analysis features in the system, discrimination accuracy improved to 98.4%. The generalization of the proposed system to unseen data converged to an overall prediction accuracy of 86.7% ± 5.4%. Considering that histological grading affects treatment selection and diagnostic errors may be notable in clinical practice, the utilization of the proposed system may safeguard against diagnostic misinterpretations in every day clinical practice.

Expression and distribution of aggrecanases in human larynx: ADAMTS-5/aggrecanase-2 is the main aggrecanase in laryngeal carcinoma.

Members of the ADAMTS family of proteases degrade proteoglycans and thereby have the potential to alter tissue architecture and regulate cellular functions. Aggrecanases are the main enzymes responsible for aggrecan degradation, due to their specific cleavage pattern. In this study, the expression status, the macromolecular organization and localization of ADAMTS-1, ADAMTS-4/aggrecanase-1 and ADAMTS-5/aggrecanase-2 in human normal larynx and laryngeal squamous cell carcinoma (LSCC) were investigated. On mRNA level, the results showed that ADAMTS-4 was the highest expressed enzyme in normal larynx, whereas ADAMTS-5 was the main aggrecanase in LSCC presenting a stage-related increase up to stage III (8-fold higher expression compared to normal), and thereafter decreased in stage IV. Accordingly, immunohistochemical analysis showed that ADAMTS-5, but not ADAMTS-4, was highly expressed by carcinoma cells. Sequential extraction revealed an altered distribution and organization of multiple molecular forms (latent, activated and fragmented forms) of the enzymes within the cancerous and their corresponding macroscopically normal laryngeal tissues, compared to the normal ones. Importantly, these analyses indicated that critical macromolecular changes occurred from the earliest LSCC stages not only in malignant parts of the tissue but also in areas that were not in proximity to carcinoma cells and appeared otherwise normal. Overall, the results of the present study show that ADAMTS-5/aggrecanase-2 is the main aggrecanase present in laryngeal carcinoma suggesting a critical role for the enzyme in aggrecan degradation and laryngeal tissue destruction during tumor progression.

Expression of the epidermal growth factor system in endometrial cancer.

The aim of our study was to describe the expression of c-erbB-1, c-erbB-2, c-erbB-3 and c-erbB-4 in endometrial cancer tissue and its correlation with clinicopathologic features and prognosis of the patients. One hundred and six cases of endometrial cancer were identified from the archives of the Department of Obstetrics and Gynecology of the University of Patras. Tissue specimens from endometrial lesions were immunostained for c-erbB-1, c-erbB-2, c-erbB-3 and c-erbB-4. Statistical analyses were performed using the chi square test, Kaplan-Meier method and Cox analysis. We found a significant association between c-erbB-1 expression and patient survival. A reverse correlation was found between tumor grade and c-erbB-1 expression. Tumor grade was not significantly correlated with the expression of the remaining three receptors. Stage of the tumor showed no relationship with the expression of these receptors. The ability to predict increased risks of advanced disease, recurrence, and death from abnormal molecular markers detected in curettage or endometrial biopsy specimens will facilitate pretreatment referral of these patients to gynecologic oncologists for definitive surgical treatment.

Expression of metalloproteinases and their tissue inhibitors in squamous cell laryngeal carcinoma.

The hallmark of cancer invasion is the degradation of extracellular matrix components. Matrix metalloproteinases are the major enzymes participating in this event and their activity is regulated extracellularly by their presence as proenzymes and the concomitant presence of the specific tissue inhibitors. The present study describes the immunohistochemical localization of gelatinases, matrix metalloproteinase (MMP)-2 and -9 and tissue inhibitor of metalloproteinase (TIMP)-1 and -2 in human laryngeal carcinoma and their expression with respect to tumor classification and compared with the respective healthy subjects. MMP-2 was immunolocalized in the cytoplasm of the epithelial cells and in the loose connective tissue, whereas MMP-9 was also observed in basement membrane and chondrocytes. Both were also found in tumor cells, but staining was decreased with increasing stage of cancer. TIMP-1 was present exclusively in stroma and totally absent from tumor cells and it was overexpressed in normal cells surrounding the tumor. TIMP-2 was identified in the cytoplasm of epithelial cells, in stroma and sometimes in chondrocytes. In addition, it was present in tumor cells of only stage IV samples. The expression level of both gelatinases and TIMPs increased as the stage of cancer increased, suggesting the possible post-transcriptional removal of their mRNA. These observations, performed in a given head and neck site, suggest that the behavior of head and neck tumors seems to depend on the site and additional studies should be performed to obtain a general understanding of the disease and ascertain the role of the constituents examined.

Expression of the epidermal growth factor system in endometrial cancer after adjuvant tamoxifen treatment for breast cancer.

The aim of our study was to describe the expression of cerbB-1, cerbB-2, cerbB-3 and cerbB-4 in endometrial cancer tissue and its correlation with clinicopathologic features and prognosis of endometrial cancer patients diagnosed during or after tamoxifen treatment for breast cancer. Thirteen tamoxifen-related endometrial cancers were identified from the archives of the Department of Obstetrics and Gynecology of the University of Patras, Medical School. Tissue specimens from endometrial lesions were immunostained for cerbB-1, cerbB-2, cerbB-3 and cerbB-4. For cerbB-1, five cases were positive and eight were negative. For cerbB-2, ten cases were positive and three were negative. For cerbB-3, nine cases were positive and four were negative. For cerbB-4, eight cases were positive and five were negative. However, a limitation of our study is that the number of cases was small, and further investigations are necessary to allow a more focused evaluation of cerbB-1, cerbB-2, cerbB-3 and cerbB-4 status, as a prognostic factor for endometrial cancer after tamoxifen treatment.

Versican but not decorin accumulation is related to metastatic potential and neovascularization in testicular germ cell tumours.

AIMS: To investigate the expression of versican and decorin in patients with testicular germ cell tumours (GCTs) and to correlate this with the clinicopathological findings. Matrix proteoglycans versican and decorin are frequently overexpressed in various malignancies and are involved in the progression of cancer. METHODS AND RESULTS: Overexpression of versican and decorin was detected in GCTs by immunoblotting. Immunohistochemical staining for proteoglycans was performed on 71 cases of paraffin-embedded tissues. In most of the cases increased decorin and versican stromal staining was demonstrated. In both seminomas and non-seminomatous germ cell tumours (NSGCTs) strong staining of decorin was not found to be related to any of the clinicopathological variables. Accumulation of versican was found to be associated with vascular and lymphatic invasion, nodal metastasis and disease stage in seminomas and NSGCTs and, in addition, with tumour size and distant metastasis only in NSGCTs. Additionally, only the deposition of versican was linearly correlated with the number of microvessels in the tumour stroma in GCTs. CONCLUSIONS: Ectopic versican and decorin expression is a frequent feature in GCTs. Versican but not decorin accumulation in GCTs is related to metastatic potential and neovascularization and might be a useful marker for testicular malignancy.

Assessment of c-erbB 3 and c-erbB 4 expression in breast cancer patients and correlation with clinicopathological parameters

Objetive: ErbB Receptor Tyrosine Kinases possess an establishedrole in mammary gland development and breast tumorigenesis.We aimed to assess the expression of c-erbB3and c-erbB4 RTKs in early breast carcinomas and investigateits possible correlation with Estrogen or Progesterone Receptors,tumor stage and grade, disease recurrence and patient’soutcome.Patients and methods: Forty-nine specimens of earlybreast carcinomas deriving from patients that had sustainedpartial or total mastectomy with axillary lymph node resectionwere studied retrospectively. Expression of RTKs was detectedimplementing: a) an anti-HER-3 mouse polyclonal antibody;and b) an anti-HER-4 mouse polyclonal antibody. For both cerbB3and c-erbB4, either a cytoplasmic or a nuclear stainingpattern of tumor cells was considered positive.Results: Expression of c-erbB4 exhibited statistically significantassociation with tumor grade and unfavorable patient’soutcome. C-erbB3 expression did not correlate with tumorrecurrence or patient’s outcome.No association was established between the expression ofboth RTKs and that of Estrogen or Progesterone Receptors.C-erbB4 expression did not posess statistically significant associationwith patient’s death or disease recurrence. C-erbB3 expressiondid not correlate with tumor grade or recurrence andpatient’s death.Conclusions: In the context of compound molecularmechanisms, alterations in c-erbB3 and c-erbB4 expressionmerit appraisal as future interventions in breast cancer treatmen (AU)

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Synchronous primary endometrial and ovarian cancers: a case report.

Synchronous primary cancers of the endometrium and ovary are relatively uncommon in the general population. The patient, a 49-year-old postmenopausal Greek woman, presented with abdominal pain and a pelvic mass. She underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy, total omentectomy, appendectomy and pelvic lymph node dissection. The histopathology revealed synchronous primary cancers of the endometrium and right ovary. She underwent postoperative chemotherapy. Thirty-nine months after surgery, she remains well without evidence of recurrence.

Suprasellar and intrasellar paragangliomas.

Neoplasms of the sellar region are entities with a large differential diagnosis. Although paraganglionic cells have not been demonstrated in the pituitary or adjacent structures, the existence of sellar region paragangliomas is well-documented. To elucidate, in this area the nature of these unusual tumors is relatively difficult. Clinical history, physical examination, radiographic investigation as well as intraoperative gross observation are the same as those of sellar meningioma or pituitary adenoma. Immunohistochemistry, using neuroendocrine markers and electron microscopy are the two definitive diagnostic methods to differentiate among these entities. The clinical management, the possible pathogenesis of the tumor, the importance of immunohistochemistry in making the diagnosis and the clinical outcome of these patients are discussed.

Expression of HIF-1alpha and iNOS in astrocytic gliomas: a clinicopathological study.

BACKGROUND: Hypoxia-inducible-factor-1 (HIF-1) is present at high levels in human tumors and plays a crucial role in tumor promotion by up-regulating several target genes. HIF-1 stimulates the production of NO through the induction of inducible NO synthase (iNOS). PATIENTS AND METHODS: Sixty-three human astrocytic gliomas were analyzed by immunohistochemistry for HIF-1alpha and iNOS using formalin-fixed paraffin-embedded material. In 39 cases, the results of immunohistochemistry were correlated with the clinical outcomes. RESULTS: HIF-1alpha was detected only in astrocytic gliomas grades III and IV, both in the nucleus and in the cytoplasm. The iNOS expression was increased in astrocytic gliomas grades I, II and III and was statistically significantly decreased in astrocytic gliomas grade IV. iNOS was localized round the capillary vessels as well. Statistical analysis showed that the HIF-1alpha and iNOS expressions did not correlate with patient survival. CONCLUSION: We believe that HIF-1alpha and iNOS expressions merit further investigations in order to understand the biology of astrocytic gliomas. More data are needed from prospective studies.

Primary peritoneal psammocarcinoma: a case presenting synchronously with bowel carcinoma.

BACKGROUND: Psammocarcinomas are rare epithelial tumors usually originating from the ovarian surface epithelium or the peritoneum. In our case, a peritoneal psammocarcinoma was incidental surgical finding during laparotomy. CASE: An 83-year-old woman underwent surgery for bowel obstruction. Intraoperativelly, a bowel carcinoma was documented. Notable were numerous small disseminated peritoneal nodules that studded the omentum and bowel serosa. At reintervention, similar nodules were observed in the serosal surface of the two ovaries, uterus, left salpinx, and omentum. The nodules corresponded histologically to psammocarcinoma of peritoneal origin. Despite not receiving adjuvant treatment, the patient is still alive 53 months following the second operation, without signs of metastases or disease recurrence. CONCLUSION: Though unpredictable, psammocarcinomas might run an indolent course, and decisions regarding management should be individualized.

Correlation of mammographic appearance and molecular prognostic factors in high-grade breast carcinomas.

The aim of our study was to evaluate the association between the mammographic appearance and the biologic characteristics of high-grade breast carcinomas. Three hundred and twenty patients with breast carcinomas were studied. Histological examination showed 83 (26%) high-grade ductal carcinomas. Immunohistochemistry was carried out by using antibodies against estrogen receptor (ER), progesterone receptor (PR), HER-2/neu, p53 and cathepsin D. In 60/83 high-grade carcinomas we studied the mammographic appearance. Asymmetric density with poorly defined margins without microcalcifications was the major mammographic finding in 49/60 (approximately 82%) high-grade ductal carcinomas. HER-2/neu positivity (68.7%) and p53 positivity (48.2%) were statistically correlated with asymmetric density with poorly defined margins without microcalcifications in high-grade carcinomas. We observed loss of ER and PR receptors in 50%, whereas loss of PR receptors was observed in 65% of high-grade breast carcinomas. Cathepsin D (> 20%) was detected in 38.5% of high-grade carcinomas. Our findings suggest a significant relationship between mammographic appearance and biologic markers in high-grade breast carcinomas.

Immunohistochemical detection of HPV proteins and c-erbB receptors in cervical lesion specimens from young women.

The intention of the present study was to assess immunohistochemically the expression of c-erbB receptor family in cervical carcinoma specimens of young women. Simultaneously, HPV was detected in the same specimens using immunohistochemical assays. Seventy-five cervical intraepithelial and invasive cancer specimens were assessed retrospectively. Positive c-erbB-2 immunostaining was revealed in 11.7% of tumor specimens, while for c-erbB-3 and c-erbB-4 receptor the corresponding figures were 32% and 49.3%, respectively. Concerning HPV infection-markers, positive immunostaining was found in 31% of cases, while coilocytes were detected in 64% of patients. The correlation of c-erbB receptor expression with malignant aggressiveness in cervical cancer cells concurs with similar data regarding other neoplasias, thus rendering these receptors an important predictive factor and future therapeutic target.

Advanced soft computing diagnosis method for tumour grading.

OBJECTIVE: To develop an advanced diagnostic method for urinary bladder tumour grading. A novel soft computing modelling methodology based on the augmentation of fuzzy cognitive maps (FCMs) with the unsupervised active Hebbian learning (AHL) algorithm is applied. MATERIAL AND METHODS: One hundred and twenty-eight cases of urinary bladder cancer were retrieved from the archives of the Department of Histopathology, University Hospital of Patras, Greece. All tumours had been characterized according to the classical World Health Organization (WHO) grading system. To design the FCM model for tumour grading, three experts histopathologists defined the main histopathological features (concepts) and their impact on grade characterization. The resulted FCM model consisted of nine concepts. Eight concepts represented the main histopathological features for tumour grading. The ninth concept represented the tumour grade. To increase the classification ability of the FCM model, the AHL algorithm was applied to adjust the weights of the FCM. RESULTS: The proposed FCM grading model achieved a classification accuracy of 72.5%, 74.42% and 95.55% for tumours of grades I, II and III, respectively. CONCLUSIONS: An advanced computerized method to support tumour grade diagnosis decision was proposed and developed. The novelty of the method is based on employing the soft computing method of FCMs to represent specialized knowledge on histopathology and on augmenting FCMs ability using an unsupervised learning algorithm, the AHL. The proposed method performs with reasonably high accuracy compared to other existing methods and at the same time meets the physicians' requirements for transparency and explicability.

Vaginal cancer in a patient treated for cervical intraepithelial neoplasia (CIN 3): case report.

In 1% to 3% of patients with cervical intraepithelial neoplasia (CIN), vaginal intraepithelial neoplasia (VAIN) will either coexist or occur at a later date. The time interval from an earlier diagnosis of CIN 3 to a current diagnosis of VAIN 3 varies from two to 17 years. Invasive vaginal cancer occurred in a woman five years after total abdominal hysterectomy for cervical intraepithelial neoplasia. In women who have undergone total hysterectomy for cervical intraepithelial neoplasia or cervical cancer, postoperative cytologic and colposcopic follow-up of the vagina is necessary.

Involvement of dysadherin and E-cadherin in the development of testicular tumours.

Testicular neoplasms are comprised of a variety of histologically different forms, and their pathogenesis has not been elucidated. Dysadherin is a recently described cell membrane glycoprotein, which has an anticell-cell adhesion function and downregulates E-cadherin. In this study, we examined immunohistochemically the expression of E-cadherin and dysadherin in 120 testicular neoplasms (37 seminomas-26 classic, five spermatocytic and six anaplastic-, 45 embryonal carcinomas, 10 mixed germ cell tumours, two yolk sac tumours, 10 mature and eight immature teratomas and eight non-Hodgkin B-cell lymphomas), clinical stage I. The intensity, the expression pattern and the percentage of neoplastic cell staining was recorded and correlated with the histologic type and vascular/lymphatic invasion. Dysadherin was not expressed in non-neoplastic germ cells, neither in CIS/ITGCNU, but it was highly expressed in all types of germ cell tumours, that demonstrated either embryonic phenotype or somatic differentiation, in most terminally differentiated neoplasms, and in all lymphomas. Dysadherin expression did not correlate with vascular invasion. Increased dysadherin expression was correlated with aberrant E-cadherin expression in most tumours. In 17% of embryonal carcinomas colocalisation of dysadherin and membranous E-cadherin staining was noted. This is the first report on dysadherin expression and its association with E-cadherin in testicular tumours. Since dysadherin is not normally expressed in non-neoplastic testis, it is conceivable that it plays a role in the neoplastic transformation of germ cells. In testicular tumours, as in other neoplasms, dysadherin downregulates E-cadherin expression, at least in part.

Leiomyosarcoma of the vulva: a case report.

Primary sarcoma of the vulva is a rare tumor. Leiomyosarcoma is the most common histologic variant of vulvar sarcoma. The patient, a 55-year-old, gravida 4, para 2 postmenopausal Greek woman, presented with a 5-year history of progressive enlargement of the right labia majora. On vaginal examination there was a 8 x 9 cm raised, ulcerated and irregular mass of the right labia majora. Despite surgery, the patient died six months later because of multiple metastases.

Primary malignant melanoma of the vagina: a case report.

Primary malignant melanoma of the vagina is a very rare, but very aggressive tumor. We describe a case of primary vaginal melanoma and review the literature. The patient, a 73-year-old, gravida 2, para 2 postmenopausal Greek woman, presented with abnormal vaginal bleeding for 30 days. On vaginal examination there was a 5.5 x 5 x 2 cm raised, ulcerated and irregular lesion on the posterior vaginal wall. Pathology examination of the entire specimen demonstrated a nodular vaginal melanoma. The histologic diagnosis was confirmed by positive immunostaining. The patient began postoperative immunotherapy with interferon-a2b. She died 25 months later because of cerebral metastases. In conclusion, the prognosis of vaginal melanoma is very poor, despite the treatment modality, because most cases are diagnosed at a late stage.

An image-analysis system based on support vector machines for automatic grade diagnosis of brain-tumour astrocytomas in clinical routine.

An image-analysis system based on the concept of Support Vector Machines (SVM) was developed to assist in grade diagnosis of brain tumour astrocytomas in clinical routine. One hundred and forty biopsies of astrocytomas were characterized according to the WHO system as grade II, III and IV. Images from biopsies were digitized, and cell nuclei regions were automatically detected by encoding texture variations in a set of wavelet, autocorrelation and parzen estimated descriptors and using an unsupervised SVM clustering methodology. Based on morphological and textural nuclear features, a decision-tree classification scheme distinguished between different grades of tumours employing an SVM classifier. The system was validated for clinical material collected from two different hospitals. On average, the SVM clustering algorithm correctly identified and accurately delineated 95% of all nuclei. Low-grade tumours were distinguished from high-grade tumours with an accuracy of 90.2% and grade III from grade IV with an accuracy of 88.3% The system was tested in a new clinical data set, and the classification rates were 87.5 and 83.8%, respectively. Segmentation and classification results are very encouraging, considering that the method was developed based on every-day clinical standards. The proposed methodology might be used in parallel with conventional grading to support the regular diagnostic procedure and reduce subjectivity in astrocytomas grading.

Normal colposcopy following abnormal Pap smear evoking LGSIL: a follow-up study.

The aim of this study was to determine the optimal treatment policy in women presenting with an abnormal Pap smear showing low-grade squamous intraepithelial lesion (LGSIL), who additionally had normal colposcopic findings. We prospectively studied 160 women with LGSIL and normal colposcopy, and divided them into two groups. Group A, consisting of 54 women, was followed-up for a mean period of 42 months and had a new control smear 12 months after the initial one. Group B, consisting of 106 women, was followed-up for a mean period of 44 months and had two consecutive control smears (6 and 12 months after the initial), and a new colposcopy, depending on the findings. At the end of the first year, the lesion persisted in 37% and 39% of the patients in groups A and B, respectively. At the end of the study, regression or persistence of the LGSIL was revealed in 63% and 61% of the women in groups A and B, respectively. Aggravation of the lesions occurred after 16.5 and 15 months, respectively, in groups A and B. Our findings suggest that women with LGSIL and normal colposcopy do not need further therapeutic measures during the first year after the initial smear.