Overexpression of p53, c-erbB-2 and epidermal growth factor receptor in human breast carcinomas

Overexpression of p53 protein, epidermal growth factor receptor (EGF-R), and c-erbB-2 protein was assessed by immunohistochemical staining of formalin-fixed, paraffin-embedded tissue from 64 invasive breast tumors. The correlation between abnormal expression of each protein and various disease parameters, including lymph node metastasis and histopathologic type and grade was analyzed. Despite the previous proposal, no significant correlation was found between lymph node metastases and overexpression of each gene in the primary tumors. In addition, some metastatic lesions did not always exhibit overexpression, even if it was evident in the primary tumors. Overexpression of c-erbB-2 protein correlated well with Bloom's histological grading. p53 expression was detected most often in tumors with hyperchromatism and more frequent mitosis. Overexpression of c-erbB-2 protein occurred more frequently in p53-positive tumors. The results indicate that abnormal expression of p53 protein causes genetic instability in the early stage of tumor development, resulting in subsequent overexpression of other oncogenes.     

Concomitant and isolated expression of TGF-alpha and EGF-R in human hepatoma cells supports the hypothesis of autocrine,paracrine, and endocrine growth of human hepatoma

Single and double immunohistochemical staining for transforming growth factor (TGF)-alpha and epidermal growth factor-receptor (EGF-R) was done in order to identify the localization of TGF-alpha and EGF-R in human hepatocellular carcinoma (HCC). Single immunohistochemical staining for TGF-alpha showed immunoreactivity in the cytoplasm of hepatoma cells in 22 of 30 cases of HCC. The localization of TGF-alpha was heterogeneous from HCC cells to HCC cells. In the surrounding regenerative nodules, the hepatocytes were mildly to moderately positive for TGF-alpha. The proliferating bile ductules and peripheral nerves were also immunopositive for TGF-alpha. Single immunohistochemical staining for EGF-R demonstrated a linear localization of EGF-R along the cell membrane of the HCC cells in 21 of the 30 cases of HCC. In the regenerative nodules, the hepatocytes also showed linear staining along the cell membrane. Double staining for TGF-alpha and EGF-R in 12 cases of HCC showed a concurrent localization of TGF-alpha and EGF-R in some hepatoma cells and isolated localization of the two substances of other HCC cells. These combinations either abruptly moved around or intermingled with each other. These immonohistochemical results thus support the theory of an autocrine, paracrine, and endocrine mechanism of TGF-alpha and EGF-R on the proliferation of human hepatocellular carcinoma. © 1995 Wiley-Liss, Inc.     

表皮生长因子受体在大肠癌及癌前病变组织中的研究

用抗表皮生长因子受体（ＥＧＦＲ）的单抗和免疫组化ＡＢＣ法，对正常大肠粘膜，大肠腺瘤伴异型增生及大肠腺癌进行标记，发现正常大肠粘膜全部为阴性，大肠腺瘤伴异型增生则有较高的表达率，而一旦癌变后，表达率有所下降，ＥＧＦＲ的表达与大肠腺癌的低分性及高浸相关，ＥＧＦＲ表达的肿瘤易发生淋巴结转移，研究结果提示，ＥＧＦＲ的表达与大肠癌的发生有一定关系，并可作为判断大肠癌生物学行为的一个有用指标。     

Immunohistochemical Analysis of EGF-R in Gastric Mucosa in Portal Hypertensive with Cirrhosis

Inclinicalpractice,theupperdigestivetracthemorrhage(UDTH)causedbygastricmucosalesion(GML)duringportalhypertension(PHT)alreadyhasbeendrawingtheattentionofcliniciansandresearchers.AlotofstudiesshowedthatthedevelopmentofGMLduringPHTwasrelatedtomanyfactorsandtheimpairmentordestructionofdefensemechanismisoneofthemaincauses.ThecombinationofEGFandEGF-Rhasanobviousprotectiveeffectongastricmucosa,soitisimportanttostudythechangeincontentofEGF--RduringPHT.Inthisstudy,thePAPixnmunohistochemic…     

Inhibition of bile salt-induced apoptosis by cyclic AMP involves serine/threonine phosphorylation of CD95

BACKGROUND AND AIMS: Cyclic AMP (cAMP) inhibits bile salt-induced hepatocyte apoptosis; the underlying mechanisms are unclear. METHODS: The effects of cAMP on taurolithocholate-3-sulfate-(TLCS)- or glycochenodesoxycholate (GCDC)-induced CD95 (Fas/APO-1) activation and apoptosis were studied in 24-hour cultured rat hepatocytes and in perfused rat liver. RESULTS: TLCS induced a rapid oxidative stress response, c-Jun-N-terminal kinase (JNK) and epidermal growth factor (EGF) receptor (EGF-R) activation, subsequent EGF-R/CD95 association and CD95 tyrosine phosphorylation, CD95 membrane targeting, death-inducing signal complex (DISC) formation and hepatocyte apoptosis. None of these responses was triggered by cAMP; however, cAMP induced H89-sensitive serine/threonine phosphorylation of CD95. Similar data were obtained with GCDC, another proapoptotic bile acid. cAMP did not prevent the TLCS-induced oxidative stress response, JNK activation and EGF-R/CD95 association, however abolished EGF-R activation and subsequent CD95 tyrosine phosphorylation, CD95 membrane trafficking, and DISC formation in a H89-sensitive way. Also in presence of TLCS, cAMP induced rapid Ser/Thr phosphorylation of CD95 within 10 min. The effects of cAMP on the various steps of CD95 activation were also found in the intact perfused rat liver. Evidence is given that a cAMP-induced Ser/Thr phosphorylation favors internalization of CD95. CONCLUSIONS: Inhibition of bile salt-induced apoptosis by cAMP involves both PKA-dependent Ser/Thr phosphorylation of the CD95 and inhibition of EGF-R activation, which results in an inhibition of CD95 tyrosine phosphorylation, CD95 membrane targeting, and DISC formation. CD95 regulation involves complex phosphorylations with CD95-tyrosine phosphorylation favoring CD95 membrane trafficking and DISC formation, whereas CD95 Ser/Thr phosphorylation inhibits these processes.     

p53 protein, EGF receptor, and anti-p53 antibodies in serum from patients with occupationally derived lung cancer.

The oncogene product epidermal growth factor receptor (EGF-R), the tumour suppressor gene product p53 and anti-p53 antibodies are detectable in the serum of certain cancer patients. Increased levels of some of these products were reported in lung cancer patients after occupational asbestos exposure and after exposure to polycyclic aromatic hydrocarbons or vinylchloride. In the first step, this study investigated the possible diagnostic value of serum EGF-R, p53-protein and anti-p53 antibodies, measured by an enzyme-linked immunosorbent assay, in lung tumour patients. In addition to being investigated on a molecular epidemiological basis, these parameters were examined as biomarkers of carcinogenesis, especially with regard to asbestos incorporation effects or of radon-induced lung cancers. Also, a possible effect of cigarette smoking and age dependence were studied. A total of 116 male patients with lung or pleural tumours were examined. The histological classification was four small-cell cancers, six large-cell cancers, 32 adenocarcinomas, 47 squamous carcinomas, 12 mixed lung carcinomas, five diffuse malignant mesotheliomas and ten lung metastasis of extrapulmonary tumours. Twenty-two lung cancers and all mesotheliomas were related to asbestos, 22 lung cancers were related to ionizing radiation and 61 patients had cigarette smoke-related lung cancer. Besides these patients 50 male patients with non-malignant lung or pleural diseases were included; of the latter eight subjects suffered from asbestosis. Controls were 129 male subjects without any lung disease. No significantly elevated or decreased serum values for p53 protein, EGF-R, or anti-p53 antibodies as a function of histological tumour type, age, or degree and type of exposure (asbestos, smoking, ionizing radiation) could be found. The utility of p53-protein, EGF-R and anti-p53 antibodies as routine biomarkers for screening occupationally derived lung cancers is limited.     

Towards a better understanding of cellular events in Mycosis fungoides: an immunohistochemical study

In the present work, we have attempted to pay special attention to epidermal and dermal cellular events in Mycosis fungoides (MF). In the epidermis, the two dendritic cell populations, CD1+ and OKM5+, HLe-1+, the adhesion molecules OKM5 and DR on the surface of epidermal cells (Ecs), and cytoskeletal proteins were studied. CD1+ dendritic epidermal cells were generally more abundant than OKM5+, HLe-1+ ones with no interrelationship in their presence. OKM5+, HLe-1+ dendritic cells prevailed in the second stage plaques. The staining pattern with anti-spectrin polyclonal antibody gradually presented increased intensity from Pre-MF to tumor stage. The activation-proliferation related immunophenotype was also examined, as well as other useful markers, in an attempt to correlate their presence in different stages of MF. Special emphasis was given to the staining pattern with the epidermal growth factor receptor (EGF-R) monoclonal antibody against three targets: epidermal, endothelial, and lymphoid cells. The presence of Ki-67 proliferation marker in suprabasal epidermal layers and lymphoid cells in the dermal infiltrate was also of interest.