In order to study the altered Rb, bcl-2 and p53 proteins expression during laryngeal carcinogenesis and to elucidate the role of these molecules in the development and progression of the lesions, we have examined the immunohistochemical expression of these markers in a series of 41 squamous cell carcinomas, 14 cases of in situ carcinoma, 47 with epithelial dysplasia, 11 papillomas and 20 cases of keratosis. Rb protein was expressed in 69.7% (> 5% positive neoplastic cells) of squamous cell carcinomas and p53 in 40% (> 5% positive cells). There was a strong statistically significant difference for Rb, Ki-67 and PCNA immunostaining between malignant, premalignant and benign lesions, increasing from keratosis, papillomas, dysplasia to carcinoma in situ or infiltrating squamous Ca. Rb protein expression was also strongly correlated with p53, Ki-67 and PCNA, while p53 protein was strongly correlated with Ki-67 (p = 0023) and PCNA (p = 0.0031) indices, in all lesions. In conclusion Rb and p53 altered proteins expression seems to play an active role in laryngeal carcinogenesis, probably from the early phase, and is correlated with proliferative activity. Also, Rb protein expression is correlated with the progression of the lesion and could be considered as indication of poor prognosis in laryngeal lesions.
The investigation of relationship of tumour biological activity and the degree of tissue infiltrating lymphocytes (T4, T8, T6) and macrophages in bladder cancer was the purpose of this study.Tumour specimens and near and distant biopsies from 26 patients suffering from superficial bladder cancer and bladder biopsies from 6 controls were studied. Monoclonal antibodies against T helper/inducer, (CD4), T suppressor/cytotoxic (CD8), Langerhans cells (CD1a) and Monocytes/Histiocytes (LeuM5) were used for the detection of lymphocyte subpopulations. Ki67 growth fractions and recurrence rate per 100 patients-months were used for the definition of the biological activity of the tumours.The degree of tissue infiltrating lymphocytes differed significantly between controls and both groups. Larger (but not significantly different) numbers were noticed in the non recurrence compared to the recurrence group of patients.We conclude that the host's immune defence mechanism against malignant cells does not seem to produce significantly different numbers of tissue infiltrating lymphocytes in tumours of low and high aggressiveness. On the other hand the degree of lymphocyte infiltration in bladder cancer is not marked compared to controls of controls of matching age.
The Y13 259 monoclonal antibody to the ras p21 protein was used in an immunohistochemical assay to study the levels of ras p21 in human uterine lesions as compared to normal tissue. Out of 73 hysterectomies obtained we have examined ras p21 expression in separately made sections from the endometrium, the cervix and leiomyomas found in the same specimens. A total of 155 tissue sections were finally evaluated and included: 55 endometrial mucosae (normal, hyperplastic and atrophic), 13 leiomyomas, 60 cervicitis (mild, moderate and severe with or without dysplasia), 3 in situ and 7 invasive carcinoma of the cervix, 12 invasive adenocarcinoma of the endometrium and 5 endometrial adenocarcinomas, which involved the cervical canal. Out of the 73 hysterectomy specimens 27 lesions were malignant and showed elevated expression of ras p21. The remaining 128 were normal or atrophic mucosae and benign or premalignant lesions, which were mostly negative. However, all cases of severe cervicitis and dysplasias and 6 out of the 12 hyperplastic endometrial lesions were found to be moderately or highly positive. Our results suggest that elevated expression of ras oncogenes may play an important role in the development of human uterine lesions.
Screening mammography and clinical breast examination are the best tools available for the diagnosis of breast carcinomas in asymptomatic women. Many studies have attempted to determine the pathological and biological characteristic findings in screening-detected cancers. Tumor size, histologic type, cytological grading and lymph node status have an important role in estimating the biological profile of non-palpable breast cancers. Tissue tumor markers, such as proliferation markers, hormone receptors, c-erbB-2 and p53 oncoproteins, bcl-2 gene and angiogenesis-related markers do not seem to distinguish mammographically detected tumors from clinically presented cancers. Further studies are needed to assess the prognostic role of certain biological factors in well-designed clinical studies along with long follow-up of screened patients.
We examined the expression of ras p21 oncoprotein using monoclonal antibody Y13 259 and applied the streptavidin-biotin method. A total of 79 imprints of breast lesions were taken during frozen section. Our purpose was evaluation of the staining intensity, at the cellular level, without the technical disadvantages of formalin-fixed, paraffin-embedded tissues. Of the 79 imprints examined, 37 were carcinomas of ductal origin (not otherwise specified type), 8 were lobular and 3 mixed. Additionally, 20 imprints from adjacent normal tissue as well as 11 fibroadenomas (simple and hyperplastic) were assessed. Our results showed the following: (1) the positivity of all cancer cells ranged from + to + + +, (2) positivity did not show any significant difference among cancer types, (3) in increasing the tumor grade, staining intensity was increased, (4) whenever benign epithelial cells were present, their expression was low or mild, (5) only hyperplastic fibroadenomas showed weak positivity, and (6) almost all the inflammatory components were constantly negative.
This study was designed to identify the immunophenotypic characteristics of malignant soft tissue tumours, induced experimentally with benzo(a)pyrene (BaP), and to evaluate the immunohistochemical expression of the ras oncogene family and p53 onco-suppressor gene in these tumours, in association with prognostic factors. Seventy-five male Wistar rats were subcutaneous injected, dorsally, with a single dose of 10.08 mgr BaP. A solid, well-circumscribed tumour was formed at the injection site, in 70 of the animals, 80-100 days after the carcinogen's administration. The tumour as well as selected main organs were excised and studied after the animals' death. All the specimens were fixed in formalin 10%, embedded in paraffin and stained with H + E. The immunohistochemical avidin-biotin method was performed in the tumour sections, using the following monoclonal or polyclonal antibodies: vimentin, desmin, muscle specific actin (MSA), a-smooth muscle actin (SMA), myoglobin, smooth muscle myosin, a-1-antitrypsin, a-1-antichymotrypsin, S-100 protein, epithelial membrane antigen (EMA), K-ras, H-ras, Pan-ras and p53. The induced tumours of the animals were almost well-circumscribed, with a partly storiform cut surface. Histologically, their appearance was more conventional with high grade leiomyosarcomas; about half of them showed highly anaplastic areas, resembling other pleomorphic undifferentiated sarcomas. Pulmonary metastatic foci were detected in 37 animals. Immunohistochemically, all the tumours displayed positive expression of vimentin, MSA and SMA. Desmin was positively expressed in 40 tumours, smooth muscle myosin in 57 tumours and EMA in 12 tumours. All the tumours were negative for myoglobin, a-1-antitrypsin, a-1-antichymotrypsin and S-100 protein. In addition, five tumours showed a positive reaction for K-ras p21, 37 for H-ras p21, 41 for Pan-ras p21 and 14 for p53 protein. The overexpression of the oncoproteins H-ras p21 and Pan-ras p21 in these tumours was significantly associated with a non-advanced tumour stage (absence of metastatic focus). In conclusion, the histological as well as the immunophenotypic features of the induced tumours are more conventional with leiomyosarcomas mostly of high grade; many of them are "dedifferentiated". The identification of both ras and p53 gene products in these tumours indicates that alterations of these genes are common but not specific events, implicated in the tumourigenesis, which may become prognostic markers for this subtype of soft tissue sarcomas.
Although the existing evidence suggests that there is no obviously superior conservative method for treating cervical intraepithelial neoplasia (CIN), one of the most widely used is the large loop excision of the transformation zone (LLETZ).A total of 897 women who were treated with LLETZ at our colposcopy clinic from 1989 to 2000 were retrospectively studied.Forty women did not have significant cervical pathology (4.5% over-treatment rate). Clear margins of excision were obtained in 748 (88.5%) of the 845 cases of CIN or microinvasive cancers. Treatment failure rates were 4.7% for clear margins and 26.8% for involved or uncertain.LLETZ is a fast and reliable method of treating CIN and microinvasive carcinoma. Generalized cauterization of the resulting crater should be avoided and satellite HPV lesions ablated. Involved margins have a higher treatmentfailure rate, therefore a larger excision is recommended as cervical craters regenerate. Treatment in pregnant women can be delayed until postpartum provided they have adequate surveillance during pregnancy.
The evaluation of the immunohistochemical expression of epidermal growth factor receptor (EGFR), c-erbB-2 oncoprotein, proliferating indices Ki-67, and PCNA were determined on 68 primary breast carcinomas. These markers were correlated with each other and with other clinicopathological variables such as: age, tumor size? histotype, tumor grade and steroid receptors' content as well as nodal status. The monoclonal antibodies anti-human Epidermal Growth Factor Receptor (EGFR1), anti-human Ki67 (DAKO) and N13259 (Oncogene Science) were applied to paraffin and frozen tissue sections. All markers showed an heterogeneous pattern of staining. There was almost equally high staining intensity at the membranus for EGFR and c-erbB-2 in about 32% of the cases. The EGFR and c-erbB-2 positive cases were much less common in infiltrating lobular (2,2/13) rather than in ductal adenocarcinomas (21,20/55). The low grade carcinomas showed low expression of EGFR and c-erbB-2 oncoprotehl comparing with high grade ductal adenocarcinomas. A high index of Ki-67 was correlated with EGFR and c-erbB-2 membrane positivity. There was an inverse relationship between the expression of c-erbB-2 and EGFR, when compared with oestrogen receptors' content. A significant correlation was also demonstrated between EGFR and c-erbB-2 immunoreactivity with lymph node status. Our results provide evidence that the synchronous immunohistochemical detection of EGFR, c-erbB-2 and Ki-67 may be of useful significance in breast cancer patients, especially when combined with other clinicopathological variables. Furthermore the expression of EGFR and c-erbB-2 oncoprotein may affect the cell proliferation and differentiation.
Ductal carcinoma in situ (DCIS) represents a biologically and morphologically heterogeneous disease. It is characterized by a proliferation of presumably epithelial malignant cells confined within the lumens of the mammary ducts, without evidence of invasion beyond the basement membrane into the adjacent breast stroma. With the widespread use of screening mammography, a dramatic change has occurred in the frequency, management and types of DCIS detected. Historically, there has been some confusion regarding the definition of DCIS and the terminology associated with the histological types of DCIS. In this review, DCIS histopathology from a historical point of view is presented.
The immunohistochemical Cathepsin D (CD) expression of tumour and stromal cells was investigated in a series of 93 human colorectal adenocarcinomas and 22 adenomas with the intention to evaluate its prognostic significance and its contribution in the metastatic potential of colorectal cancer. CD expression was correlated with the expression of extracellular matrix components (collagen type IV, laminin and fibronectin), p53 protein, pRb, bcl-2, c-erbB-2, EGFR, proliferation indices (Ki-67, PCNA) as well as with other conventional clinicopathological features. CD expression (> 10% of positive tumour cells) was observed in 60.2% of carcinomas and in 72.7% of adenomas. Stromal CD expression was detected in all cases. A statistically significant positive correlation between neoplastic cells CD and stromal cells CD (SCCD) was observed in both carcinomas and adenomas. Cancer cells CD (CCCD) was positively correlated with collagen type IV and pRb expression as well as with PCNA score. In carcinomas, SCCD expression was statistically correlated with p53 protein and pRb expression and a trend for correlation with PCNA score was found. These data suggest that Cathepsin D of cancer and stromal cells, especially in combination with other markers, may provide more information about the biological behaviour of colorectal cancer.
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