Degree Of Histological Malignancy Research Articles

Endosialin (CD248) Expression in Fibromas and Soft-tissue Fibrosarcomas in Dogs.

Endosialin is present in human fibrosarcoma neoplastic cells. This study aimed to analyse the expression of selected cellular proteins found in fibrosarcomas and soft-tissue fibroids in dogs. A total of 71 skin tumours obtained from dogs were used. The samples included 31 fibromas and 40 fibrosarcomas. Histopathological evaluation was performed according to World Health Organization guidelines. Immunohistochemistry was performed with anti-endosialin, Ki-67, cyclo-oxygenase 2 and vimentin antibodies and assessed using the semi-quantitative scale. Endosialin expression was observed in 82.5% of fibrosarcomas and in 35% of fibromas. A significant positive correlation was found between the expression of endosialin in fibrosarcoma neoplastic cells and the degree of histological malignancy and the expression of the Ki-67 and cyclo-oxygenase 2 antigen. Expression of vimentin confirmed mesenchymal origin of this tumours. The results of our research suggest that endosialin is involved in the carcinogenesis of fibrosarcoma in dogs.

Expression of Periostin in Mammary Cancer Cells of Female Dogs.

Periostin (POSTN) has a significant role in proliferation and migration of tumour cells as well as tumour progression. This study aimed to determinate POSTN expression in cancer cells in malignant and benign tumours of the mammary gland in female dogs. All together 83 cancers, 24 adenomas and 7 unchanged fragments of the mammary glands of bitches were investigated. Immunohistochemistry was performed using anti-POSTN, Ki-67 and HER2 antibodies. POSTN expression was observed in cancer cells in 31.3% of malignancies and 12.5% of benign tumours. A significantly positive correlation between expression of POSTN in cancer cells and the degree of histological malignancy, expression of Ki-67 antigen and expression of POSTN in CAFs was found. The obtained results suggest the possible participation of POSTN in the process of carcinogenesis and progression of mammary tumors in bitches.

Primary pulmonary sarcoma - long-term treatment outcomes and prognostic factors.

IntroductionPrimary pulmonary sarcoma (PPS) is a rare type of non-epithelial malignant tumour of the lungs. Lung sarcomas are usually of metastatic character, originating from the primary tumour located in another organ. Pathomorphological diagnosis is difficult and therefore definitive diagnosis is usually determined after surgical treatment. Five-year survival of radical operated patients is 42–69%.AimTo evaluate prognostic factors in PPS.Material and methodsTwenty-two patients who underwent surgical treatment between 1994 and 2009 were analysed.ResultsTen types of sarcomas were identified. All 22 analysed patients underwent operations and in 14 (63.6%) cases it was R0 resection (pneumonectomies, lobectomies, non-anatomical resections). In 8 out of 22 patients a locally advanced form was identified. Median overall survival (OS) in the group of all patients was 22 months, 5- and 10-year OS was 27% and 18% respectively, whereas in patients who underwent non-anatomical lung resections it was 80% and 60% respectively with median OS of 213 months. Overall survival was dependent on gender, completeness of treatment and size of tumour. Haemoptysis was a poor prognostic factor. Primitive neuroectodermal tumour was a type of sarcoma with a negative effect on progression-free survival. No impact of age, type of sarcoma, degree of histological malignancy, stage or adjuvant treatment on OS was noted.ConclusionsPrimary radical surgical resection prolongs patient survival. Patients with tumours larger than 5 cm and men have worse prognoses. Future studies conducted on larger groups of patients diagnosed with PPS are necessary.

Expression of LIMS-1 Protein in Selected Cancers of the Genital Organ in Women

Aim : The study aimed atimmunohistochemical evaluation of LIMS-1 (PINCH-1-cysteine-histidine-rich) protein expression and localization in squamocellular cancer of uterine cervix, grades IB1 (T1b) and IIIB, in endometrial cancer, grades IB (T2b, NO, MO) and IIIB (T1, T2, T3, N1, MO) and in serous ovarian cancer, grades IB (pT1b) and IIIB (pT3b). Methods : The immunohistochemical studies were conducted in paraffin sections, using rabbit polyclonal antibodies specific for LIMS-1 (Sigma R ), diluted 1/200. The reaction was developed using EnVision IM FLEX DAB + Chromogen DAB solution. The expression was evaluated using modified IRS scale according to Remmele. Statistical analysis involved application of Kolmogonov–Smirnov test of normal distribution, Kruskall–Wallis test, analysis of K–means cluster and R-Spearman test. Results : there was no relationship between the expression of LIMS-1 and the advancement of neoplastic disease according to FIGO classification in squamocellular cancer of uterine cervix: the significance coefficient in the chi-square test amounted to p = 0.086. In cases of endometrial cancer and ovarian cancer, the relationship between these variables showed the level of significance to be p = 0.045 and p = 0.041, respectively. In the cases where the chi-square test demonstrated a relationship between the stage of FIGO classification and the LIMS-1 expression, the R correlation coefficients of Spearman presented values of 0.66 (p=0.003) for endometrial cancer and 0.88 (p=0.005). Conclusion : Increase in expression level of LIMS-1 protein in studied neoplasms was demonstrated to manifest positive correlation with degree of histological malignancy according to FIGO, or with neoplastic progression.

The role of neoadjuvant chemotherapy of triple-negative breast cancer in St. Petersburg City Clinical Oncological Dispensary

Introduction. Triple-negative breast cancer (BC) is very aggressive form of breast malignancies with high levels of dissemination, frequent ecurrence and poor survival rate, as compared to other breast cancer subtypes. Aim of the study – development and introduction of optimized treatment strategy of patients with triple-negative breast cancer into the clinical practice of City Clinical Oncological Dispensary. Materials and methods . The study included 201 patients (21–90 years, mean age 52 years) who were treated in the first department of St. Petersburg City Clinical Oncological Dispensary from 2005 to 2011. Stage IА–IIIC invasive breast cancer with triple-negative phenotype according to immunohistochemical study of the tumor material was verified in all the patients before beginning of the treatment. Standard chemotherapy by FAC, CMF and taxane-containing regimen was used as neoadjuvant chemotherapy. The degree of therapeutic pathomorphism was evaluated according to Miller-Payne (2003) classification, which was designed taking into account an overall survival rate of patients, depending on the degree of pathologic tumor regression. Results. We performed evaluation of 3-year relapse-free survival, depending on the degree of pathomorphological regression and histological degree of malignancy. There is a clear dependence of the 3-year relapse-free survival on the degree of histological differentiation of the tumor. We noted an inverse correlation between high degree of histological malignancy with a short relapse-free period. The disease progressed in patients who have a high degree of histological malignancy. Conclusion . The highest efficiency was achieved in patients receiving chemotherapy with the addition of taxanes. It is advantageous to include taxane-containing chemotherapy regimens in the treatment of patients with a high degree of histological malignancy.

Extracellular matrix in tumours as a source of additional neoplastic lesions - a review

Abstract The review describes the role of cells of extracellular matrix (ECM) as a source of neoplastic outgrowths additional to the original tumour. The cells undergo a spontaneous transformation or stimulation by the original tumour through intercellular signals, e.g. through Shh protein (sonic hedgehog). Additionally, cells of an inflammatory infiltrate, which frequently accompany malignant tumours and particularly carcinomas, may regulate tumour cell behaviour. This is either by restricting tumour proliferation or, inversely, by induction and stimulation of the proliferation of another tumour cell type, e.g. mesenchymal cells. The latter type of tumour may involve formation of histologically differentiated stromal tumours (GIST), which probably originate from interstitial cells of Cajal in the alimentary tract. Occasionally, e.g. in gastric carcinoma, proliferation involves lymphoid follicles and lymphocytes of GALT (gut-associated lymphoid tissue), which gives rise to lymphoma. The process is preceded by the earlier stage of intestinal metaplasia, or is induced by gastritis alone. This is an example of primary involvement of inflammatory infiltrate cells in neoplastic progression. Despite the numerous histogenetic classifications of tumours (zygotoma benignum et zygotoma malignum, or mesenchymomata maligna et mesenchymomata benigna), currently in oncological diagnosis the view prevails that the direction of tumour differentiation and its degree of histologic malignancy (grading) are more important factors than the histogenesis of the tumour.

Cervical lymph node metastasis in oral squamous cell carcinoma: A correlative study between histopathological malignancy grading and lymph node metastasis

Histologic grading has been used as a prognostic factor and for clinical behavior evaluation of oral squamous cell carcinoma for the past several decades. At the same time, the prognostic value of different grading classifications remains controversial. A major problem for most histopathological grading systems is the intraobserver and interobserver disagreement. To validate the prognostic efficiency of the histologic assessment of the primary tumor in predicting cervical metastasis, to identify those histologic features in the tumor most closely associated with cervical metastasis and to evaluate the reliability of the multifactorial grading (MFG) system by measuring intraobserver and interobserver agreement using kappa statistic. A set of 60 cases were chosen at random out of the 292 squamous cell carcinoma cases reported in our institution from 2007 to 2010. All cases were graded according to: Modified Broders' descriptive system and Anneroth et al., MFG system. Two Pathologists independently graded the tumor forefront blinded to the node metastasis. The MFG showed a significant relation between the degree of histologic malignancy and presence of metastasis in the nodes. Among the components of grading, a significant difference was observed in the nuclear polymorphism and the pattern of invasion between the metastatic and non-metastatic patients. Intraobserver and interobserver agreement was acceptable and satisfactory. Moderate to good agreement between observers greatly increases the validity of the MFG system. The multifactorial malignancy grading could serve as a predictor for metastasis in the cervical lymph nodes.

Mucosal cutting biopsy technique for histological diagnosis of suspected gastrointestinal stromal tumors of the stomach

The Japanese Gastrointestinal Stromal Tumor (GIST) therapeutic guidelines recommend endoscopic ultrasound-guided fine-needle aspiration biopsy for histological diagnosis. However, before 2010, this technique was only carried out at a minority of medical institutions in Japan. In the present study, we investigated the usefulness of mucosal cutting biopsy. In 18 asymptomatic gastric submucosal tumors, mucosal cutting biopsies were carried out. We examined tumor size, tumor site (lower third: L; middle third: M; upper third: U), histopathological diagnostic yield and complications. In cases that proceeded to surgical resection with a diagnosis of GIST, we compared the pre- and postoperative histopathological diagnosis, and the histological degrees of malignancy. The tumors had a mean size of 20.3 mm and were located at the L site in five cases, M in four, and U in nine. Histological diagnosis of submucosal tumor was obtained in all the cases. (GIST, n = 13; heterotopic pancreas, n = 2; and leiomyoma, n = 3). No complications (e.g. bleeding, perforation or peritonitis) were seen after this procedure. In all 11 patients with GIST who underwent surgical resection, the histopathological findings from the mucosal cutting biopsy specimens were similar to those from the surgically resected specimens, with agreement between the immunostaining findings and the histological degree of malignancy (90.9%) in 10 patients. The mucosal cutting biopsy technique is a useful diagnostic modality for the diagnosis of gastric GIST and for selection of the appropriate treatment.

Relationship between receptors for insulin-like growth factor - I, steroid hormones and apoptosis-associated proteins in canine mammary tumors

In the veterinary literature there are few data concerning the expression of insulin-like growth factor type I (IGF-IR) in the canine mammary gland tumors. The aim of the present study was the evaluation of IGF-IR expression and its correlation to the expression of estrogen receptor alpha (ERalpha) and progesterone receptor (PR), proteins: Bcl-2, Bax, p53 in canine mammary gland tumors, and also a correlation with other features: bitch's age, tumor diameter, histologic type of tumor, degree of histologic malignancy, proliferate activity. The study was done on 112 epithelial neoplasms: 21 (19%) were adenoma, 38 (34%) complex carcinoma (adenocarcinoma), 47 (42%) simple carcinoma (adenocarcinoma) and 6 (5%) solid carcinoma. Histochemistry and immunohistochemistry methods were employed. It was shown that more common and/or higher IGF-IR expression in cells of canine mammary gland tumors was related to the histologic type of cancer of worse prognostic (solid and simple carcinoma), high histologic degree of malignancy (III degrees) but the statistical analysis did not reveal any significant differences. We observed the high degree of IGF-IR expression in tumors which displayed the high ERalpha and PR expression. These results suggest the involvement of IGF-IR in the development of hormonosensitive canine mammary tumors. Additionally, the significant positive correlation between expression of IGF-IR and p53, Bax was found. Our study provides some evidence that interactions exist between the IGF-IR and these apoptosis-associated proteins may contribute to the development and progression of canine mammary gland tumors. These results require further investigations.

Human glioblastoma tumours and neural cancer stem cells express the chemokine CX3CL1 and its receptor CX3CR1

Human gliomas represent an unmet clinical challenge as nearly two-thirds of them are highly malignant lesions with fast progression, resistance to treatment and poor prognosis. The most severe form, the glioblastoma multiforme, is characterised by a marked and diffuse infiltration through the normal brain parenchyma. Given the multiple effects of chemokines on tumour progression, aim of this study was to analyse the expression of the chemokine CX3CL1 and of its specific receptor CX3CR1 in 36 human surgical glioma samples, with different degrees of histological malignancy and in glioblastoma-derived neurospheres. Herein we show that both ligand and receptor are expressed at the mRNA and protein levels in most specimens (31/36). While receptor expression was similarly detected in low or high grade tumours, the uppermost scores of CX3CL1 were found in grades III–IV tumours: oligodendrogliomas, anaplastic astrocytomas and glioblastomas. Accordingly, the expression of CX3CL1 was inversely correlated with patient overall survival ( p = 0.01). Glioblastoma-derived neurospheres, containing a mixed population of stem and progenitor cells, were positive for both CX3CR1 and for the membrane-bound chemokine, which was further up-regulated and secreted after TNF-IFNγ stimulation. Confocal microscopy of 3D neurospheres showed that the ligand was primarily expressed in the outer layer cells, with points of co-localisation with CX3CR1, indicating that this ligand–receptor pair may have important intercellular adhesive functions. The high expression of CXC3L1 in the most severe forms of gliomas suggests the involvement of this chemokine and its receptor in the malignant behaviour of these tumours.

An Analysis of Distant Metastases in Oral Squamous Cell Carcinoma

Metastases to distant organs are well known to be factors influencing prognosis in patients with oral cancer. Therefore, it is very important to detect the metastasis of cancer as early as possible and to investigate the factors associated with the mechanism of metastasis. This study evaluated the risk of distant metastasis by the degree of histological malignancy among 59 patients with oral squamous cell carcinoma (SCC) who were treated at our department during the past five years. The degree of histological malignancy of initial biopsy specimens was evaluated by Anneroth's classification and its relationship with metastasis was analyzed. Distant metastasis occurred in 7 of 59 patients (11.9%) and was located predominantly in the lung and bone. There was a significant correlation between the degree of histological malignancy and distant metastasis (P<0.05); however, there was no significant difference between T classification and metastasis in the distant organs. It is considered that histological malignancy is useful for predicting the prognosis and deciding additional treatments for oral SCC. When a total score on histological malignancy grading exceeds 14, metastasis in the distant organs should be carefully considered.

Overexpression of A disintegrin and metalloproteinase 28 is correlated with high histologic grade in conventional chondrosarcoma

Low-grade chondrosarcoma and enchondroma are occasionally difficult to differentiate solely by reference to clinicoradiologic and histologic findings. The A disintegrin and metalloproteinases are a new gene family of proteins having a metalloprotease domain with matrix metalloproteinases and play an important role in the chondrocyte development process. Therefore, we analyzed the expression of A disintegrin and metalloproteinases and matrix metalloproteinases in several kinds of cartilaginous bone tumors at the messenger RNA level and immunohistochemical protein level and ascertained their relationships to the histologic degree of malignancy. Reverse transciptase-polymerase chain reaction and real-time quantitative reverse transciptase-polymerase chain reaction of the expression of the A disintegrin and metalloproteinase family in cartilaginous bone tumors demonstrated that A disintegrin and metalloproteinase 28 messenger RNA levels in grade I chondrosarcoma were significantly higher than those in enchondroma (P = .009). Moreover, positive immunoreactivity of A disintegrin and metalloproteinase 28 was observed in 12 (59%) of 22 patients with grade I chondrosarcoma and in 21 (91%) of 23 patients with grade II chondrosarcoma, respectively. In contrast, only 2 (9%) of 21 cases of enchondromas demonstrated positive staining for A disintegrin and metalloproteinase 28. On the other hand, the immunohistochemical expressions of matrix metalloproteinase 9 and matrix metalloproteinase 13 were significantly higher in enchondromas than in normal cartilage tissue; however, there is no statistically different expression between enchondromas and grade I chondrosarcomas. We detected that overexpression of A disintegrin and metalloproteinase 28 was increased according to its histologic grade in conventional chondrosarcoma and could be one of the helpful tools in distinguishing between low-grade chondrosarcoma and enchondroma.

Levantamento Epidemiológico dos Casos de Carcinoma Epidermóide da Cavidade Bucal Registrados no Serviço de Diagnóstico Histopatológico do Instituto de Ciências Biológicas da Universidade de Passo Fundo/RS

The objective of this study was to make an epidemiological survey of cases of squamous cell carcinoma registered in the Histological Diagnostic Department, in the Institute of Biological Sciences of the University of Passo Fundo/RS, in the period from 1984 to 2006. A research of reports and pathological examinations diagnosed with squamous cell carcinoma was made, evaluating gender, age and race of the patients, plus the location of injuries in the mouth and their histological degree of malignancy. After the analysis of data related to the 80 identified cases, was found in male a frequency of 77,50%, the predominant age ranged from 50 to 59 years old, and was found a bigger commitment of the white race (68,70%). The lower lip was the most affected site (23,70%), followed by the oral floor (18,70%), and tongue (17,50%). About the WHO’s histological degree of malignancy, the moderately differentiated category was predominant (41,20%). The results shows that the squamous cell carcinoma occurs more often in the male gender, in the sixth decade of life, with preferencial location in the lower lip, followed by oral floor and tongue, predominating the moderately differentiated category by the point of view of histological malignancy. The knowledge of this data is essential to the dentists to obtain a profile of the patients with the entity under study, enabling the identification of the risk factors, the injuries´ prevention and the early diagnosis of suspicious injuries.

GASTRIC MALT LYMPHOMA AND HELYCOBACTER PYLORI INFECTION

Introduction: Gastric MALT lymphoma accounts aproximately 7% of all gastric tumors. Women are mostly affected by this disease (mean age 60 years). The aim of this study was to determine the incidence of gastric MALT lymphoma in the Endoscopy Unit of the Department of Gastroenterology Of University Clinical Center Tuzla, the degree of histological malignancy and correlation with the Helycobacter pylori infection and then to evaluate the effectiveness of triple-antibiotic therapy (protonic pump inhibitors and antacides) in treatment of these cases. Patients and methods: All the patiens in the study were performed with gastroscopy and mucosal tissue biopsy in the Endoscopy Unit of the Department of Gastroenterology of UKC Tuzla. PHD and IHH analysis of the given material were performed in the Patology Department of UKC Tuzla. The blood analyses on H. Pylori were done in the Department of Microbiology of UKC Tuzla. Results: 112 patients with gastric tumors were involved in this study, 91 of whom suffered from malignant tumors, six of them had MALT lymphoma (five of them had confirmed H. pylori infection, four had histologically confirmed low-grade tumors and two was categorised as high grade malignancies). Histological lesions were classified according to the actual Ann Arbor classification. Patients with high malignancy risk underwent the operative procedures, and then were treated by polychemiotherapy (CHOP protocole, VI-VIII cikluses). All the patients with confirmed H. pylori infection were treated with antibiotics for 2-4 months, after which complete eradication was accomplished in all cases. Patients histologicaly diagnosed with low grade malignancy showed complete histological regression. In addition to that, after triple antibiotic therapy none of the patients presented with the disease transformation into another histological form. Discussion and Conclusion: The results of this study prooved high incidence in use of triple antibiotic therapy in treatment of patients who suffer from MALT lymphoma with confirmed H. pylori infection. Besides, it is very important to emphasise the fact that patients had no side-effects during polychemiotherapy which was used to treat all the patients regardless of their histological type and malignancy degree of MALT lymphoma.

P27/Kip1 Expression in Gliomas and Its Clinical Significance

Objective: To study p27/Kip1 expression in gliomas and its application value. Methods: Immunohistochemical technique was used to detect the exprssion of p27/Kip1 gene in 48 different malignant grade human brain glioma tissues categorized according to WHO classification and 12 normal human brain tissues, which were analyzed quantitatively by using the image system and compared retrospectively with the patients' clinical characteristics. Results: In this series, the immunohistochemical reaction for p27/Kip1 was confined to the nuclei. The abnormal positive expression rate of p27/Kip1 in gliomas was found to be higher than that in normal tissues (P<0.05). The positive nuclei expression of p27/Kip1 decreased in number and staining intensity with the increasing degree of histological malignancy (P<0.05). Lower expression of p27/Kip1 was associated with poor prognosis (P<0.05). P27/Kip1 expression could be regarded as an independent prognostic factor. Conclusion: The abnormal expression of p27/Kip1 may be closely related to the occurrence and development of gliomas, and also can be used to evaluate the prognosis independently.

A mucinous histochemical study on malignancy of aberrant crypt foci (ACF) in rat colon.

The relationship between malignancy and number of crypts (crypt multiplicity) comprising aberrant crypt foci (ACF) was investigated, by studying changes in the mucous nature of ACF with 5 crypts or less, ACF with 6-13 crypts, adenomas and invasive adenocarcinomas induced by 1,2-dimethylhydrazine in distal colon of rats. A paradoxical Con A-staining was performed for goblet cell mucins. Of the sulfomucin-dominant ACF with 1-3 crypts, 82.6% had labile class III mucin, similar to the distal colon in the normal rats. However, in most of the goblet cell mucin produced by the ACF with 4-5 crypts with an indicated relation to colorectal carcinoma or the sialomucin (SiM) -dominant ACF with 1-3 crypts, mucin types other than class I were rarely present. The incidence of class I mucin decreased with the increase in crypt multiplicity of ACF or in the degree of histological malignancy, with the lowest incidence of 40% in adenocarcinomas. In contrast, the incidence of class II mucin increased markedly with the increase in crypt multiplicity of ACF or in the degree of histological malignancy, with the highest incidence in adenocarcinomas (95%). The ACF with 6-13 crypts had a mucous profile similar to that of adenomas. These results suggested that malignancy of ACF related to the crypt multiplicity. In the ACF with 1-3 crypts, SiM-dominant ACF had the potential to progress to malignant lesions.

Overexpression of p53 Protein Associated with Proliferative Activity and Histological Degree of Malignancy in Solar Keratosis

Background: Overexpression of p53 protein has frequently been demonstrated in human epithelial neoplasms including squamous cell carcinoma (SCC) and solar keratosis (SK). SK is a precursor lesion of SCC. In SCC of the skin, we have already reported that overexpression of p53 protein is associated with the proliferative activity, which is indicated by the percentage of Ki-67-positive cells. In SK, however, the significance of p53 overexpression is still unclear. Objective: The aim of the present study was to clarify the relationship between p53 overexpression and proliferative activity, and between p53 overexpression and histological degree of malignancy in SK. Methods: Sixty-eight cases of SK were divided into four grades according to the proportion of atypical cells in the epidermis (in grade I, up to 25% of the epidermal cells are atypical, in grade II 25–50%, in grade III 50–75%, in grade IV more than 75%) and were immunohistochemically analyzed for the expression of p53 protein and Ki-67 antigen. Results: p53 overexpression was detected in 58 out of the 68 cases of SK. The percentage of p53-protein-positive cells (DO-7 index) ranged from 0 to 78.8 (mean ± SD = 20.6 ± 21.6). Mean DO-7 indices were 7.9 in grade I, 26.7 in grade II and 38.3 in grade III. The differences in mean DO-7 index between grades I and II and between grades I and III were statistically significant (p < 0.001). The percentage of Ki-67-antigen-positive cells (MIB-1 index) ranged from 0.8 to 38.2 (mean ± SD = 10.5 ± 9.0). Mean MIB-1 indices were 5.9 in grade I, 10.7 in grade II and 20.5 in grade III. The differences in the mean MIB-1 index between grades I and II and between grades II and III were statistically significant (p < 0.01). Cases with higher DO-7 indices tended to show higher MIB-1 indices, and the relation was statistically significant [y = 0.272x + 4.8; correlation coefficient r = 0.59 > r (n – 2, 0.01) = 0.31]. Conclusion: Overexpression of p53 protein was related to cell proliferation as well as histological degree of malignancy in SK. Dysfunction of p53 protein might be implicated in skin carcinogenesis.

Relationship between Ki-67 Antigen Expression and Histological Degree of Malignancy in Squamous Cell Carcinoma of Tongue

Relationship between Ki-67 Antigen Expression and Histological Degree of Malignancy in Squamous Cell Carcinoma of Tongue

Quantitative p53-Proteinbestimmung in benignen Mammageweben, Mammakarzinomen und axillären Lymphknotenmetastasen

Die meisten Studien über die prognostische Wertigkeit der p53-Expression bei Mammakarzinomen beruhten bislang auf immunhistochemischen Methoden und führten zu sehr widersprüchlichen Ergebnissen. Hauptursache hierfür dürfte die subjektive Beurteilung der Färbeintensität des Gewebes und daher willkürliche Festlegung eines Schwellenwertes zur Trennung „p53-positiver“ von „p53-negativen“ Proben sein. Dieser subjektive Einfluß des Untersuchers wäre durch einen quantitativen p53-Proteinassay vermeidbar. In der vorliegenden Arbeit wurde ein luminometrischer Assay zur Quantifizierung der p53-Proteinkonzentrationen in Mammakar-zinomgeweben (n = 99) verwendet. Gewebeaufbereitung und Zytosolherstellung stimmten mit dem Verfahren des Abbott-Steroidrezeptorassays überein. Zur Definition einer oberen Normgrenze (Cut-Off) wurden Gewebeproben aus normalem oder benigne alteriertem Mammaparenchym (n = 40) analysiert. Zusätzlich wurden histologisch normale (n = 6) und metastatisch befallene axilläre Lymphknoten (n = 8) untersucht. Durch Bestimmung der Gesamtproteinkonzentration im Zytosol mit der Bio-Rad-Methode konnten die p53-Proteinkonzen-trationen - analog zum Rezeptorassay - in ng/mg Protein ausgedrückt werden. In den Kontrollgeweben fand sich eine breite Streuung der p53-Konzentrationen (= 0,01-0,76 ng/mg Protein, Median: 0,035 ng/mg Protein) mit einer oberen 5%-Vertrauensgrenze von 0,111 ng/mg Protein, welche als obere Normgrenze (Cut-Off) verwendet wurde. Bei qualitativer Betrachtung zeigten 66% (65/99) der invasiven Mammakarzinome sowie 5 von 8 Lymphknotenmetastasen erhöhte p53-Konzentrationen. Die relative Häufigkeit erhöhter p53-Konzentrationen zeigte eine signifikante Beziehung zum histologischen Grading der Karzinome (Gl: 36%; GII: 72%; GIII; 78%), nicht hingegen zum Nodal- oder Rezeptorstatus. Demgegenüber ergab der quantitative Vergleich der p53-Konzentrationen einen deutlichen Informationsgewinn: Die Gesamtgruppe der invasiven Karzinome zeigte signifikant höhere p53-Konzentrationen als die Kontrollgruppe (p<0.0003). In nodal-positiven und rezeptornegativen Karzinomen waren die Konzentrationen jeweils tendenziell höher als in nodal-negativen und rezeptorpositiven Tumoren, wenngleich diese Unterschiede nicht signifikant waren. Mit steigendem histologischen Malignitätsgrad fand sich ein massiver Anstieg der p53-Konzentrationen, wobei alle Unterschiede zwischen den Untergruppen Gl, GII und CIII signifikant waren (p = 0.0066-p = 0.0384). Zusammenfassend weisen Mammakarzinome höheren histologischen Malignitätsgrades deutlich höhere p53-Proteinkonzentrationen auf als Tumoren geringerer Malignität. Bei Mammakarzinomen scheint die Rate erhöhter p53-Proteinkonzentrationen deutlich höher zu sein als die von anderen Autoren berichtete Mutationsfrequenz der proteincodierenden Regionen des p53-Gens.

舌癌の増殖能に関する免疫組織化学的研究 Ｋｉ‐６７抗原発現と組織学的悪性度との関連性について

舌癌の増殖能に関する免疫組織化学的研究 Ｋｉ‐６７抗原発現と組織学的悪性度との関連性について