Immunohistochemical distribution of human epidermal growth factor in salivary gland tumours

Summary Immunohistochemical identification of human epidermal growth factor (hEGF) was carried out in a total of 152 cases of salivary gland tumours, consisting 107 pleomorphic adenomas and their variants, 13 adenolymphomas and 32 adenoid cystic carcinomas. A high percentage of pleomorphic adenomas revealed markedly positive hEGF staining of the luminal surface cells of tubuloductal structures and of modified or neoplastic myoepithelial cells. Clear cells of the tumour showed various reactivities from very slight to strong. Eosinophilic epithelial cells of adenolymphoma gave a positive reaction for hEGF in all the cases, whereas most adenoid cystic adenoma lacked hEGF staining; however some cases showed positive staining of the tumour cells. The immunohistochemical detection of hEGF in most salivary gland tumours suggests this factor to be a possible new marker of salivary glands tumours, and to have a biological role in tumour proliferation.     

Carcinosarcoma ex recurrent pleomorphic adenoma of the submandibular gland

We report a case of carcinosarcoma ex recurrent pleomorphic adenoma in the submandibular region of a 56-year-old Japanese man. He presented with a 2-year history of a rapidly growing mass in the submandibular region. He reported undergoing excision of a nodule in the same region 10 years earlier. Incisional biopsy confirmed the diagnosis of pleomorphic adenoma. The lesion was excised surgically. The resected tumor measured 40 x 20 mm and was composed of two large nodules and multiple small satellite nodules in the subcutaneous tissue. Histopathologically, one large nodule was carcinosarcoma while the other large nodules and small satellite nodules were pleomorphic adenoma. The former large nodule showed a variegated pattern with carcinomatous components (poorly differentiated adenocarcinoma, salivary duct carcinoma, squamous cell carcinoma and undifferentiated carcinoma) and sarcomatous components (spindle cell sarcoma, chondrosarcoma, liposarcoma and rhabdomyosarcoma). Based on the clinical history and histopathology, we consider the lesion to have originated from recurrent pleomorphic adenoma.     

An immunohistochemical study of bone morphogenetic protein in pleomorphic adenoma of the salivary gland

Bone morphogenetic protein (BMP) is a potent induction factor for new bone formation including heterotopic chondro-ossification in soft tissues. The immunohistochemical reaction for BMP was studied in 23 cases of pleomorphic adenoma of salivary gland by using a monoclonal antibody produced by hybridoma technique. Positive BMP immunoreactivity was seen in 87% of tumours. Immunohistochemical expression of BMP was observed in modified myoepithelial cells (88% cases), luminal tumour cells of tubulo-ductal structures (78% cases) and chondroid cells in hyaline tissue (22% cases). The authors concluded that the simultaneous presence of glycosaminoglycans as matrix substance and S-100 protein for calcium signalling are associated with BMP-mediated cellular activity of modified myoepithelial cells in the formation of chondroid structures in pleomorphic adenomas of the salivary glands.     

Subcellular localization of epidermal growth factor receptor in human submandibular gland

The subcellular distribution of the epidermal growth factor receptor (EGFr) was demonstrated in the normal human submandibular gland by means of immunogold cytochemistry. EGFr labelling appeared in both acinar and ductal cells, where strong immunoreactivity was associated with a tubulovesicular system near the basolateral surfaces. In addition, groups of reactive vesicles were highlighted among secretory granules of both serous and mucous cells and at the apex of ductal cells. Basolateral vesicles were interpreted as being a result of EGFr internalization after activation by an exogenous ligand, although the functional meaning of those located apically remains unclear.     

Pigmented pleomorphic adenoma,a novel melanin-pigmented benign salivary gland tumor

This paper reports a pleomorphic adenoma with grossly visible pigmentation resulting in the macroscopic appearance of melanotic lesion in a 33-year-old Japanese male. In addition to the characteristic histopathological features of a benign pleomorphic adenoma, variously formed and -sized cells, many of which were considered to be melanocytes, containing melanin pigment in their cytoplasm, were distributed in the epithelial component. In addition, melanin pigment was deposited in tumor cells of duct structures. Furthermore, condensed secretory substances with marked pigmentation were frequently seen in the tubular lumina. Perusal of the English language literature revealed only two cases of parenchymal pigmentation of salivary gland tumors: both were mucoepidermoid carcinoma. The possible histogenesis of melanocytes in the salivary gland lesions is discussed, though no firm conclusion could be drawn.     

Diversity of collagen expression in the pleomorphic adenoma of the parotid gland

Summary The high diversity of collagen expression and its qualitative and quantitative aspects are demonstrated in pleomorphic adenoma using electron microscopy and specific histochemical methods. Great variability was observed in the amount, distribution and characteristics of the collagen found in the various types of tissue normally present in this tumour. Both deficient polymerization and hyperpolymerization of collagen and the occurence of desmoplasia were observed. Evidence is presented to suggest a role for localized collagenolysis in the invasiveness of this neoplasia.     

The pleomorphic adenoma of salivary glands transplanted on athmymic mice

Summary 10 pleomorphic adenomas of the human parotid gland were transplanted on several groups of nude mice. For comparative reasons, 10 other pleomorphic adenomas, a neurinoma and a chordoma and transplants of squamous cell carcinomas and of normal salivary gland tissue were also analysed.In the primary tumours and in the transplants, the presence of keratin, carcinoembryonic antigen, tissue polypeptide antigen, lactoferrin, lysozyme, immunoglobulins, secretory component, amylase, fibronectin and of several lectin-receptors (PNA, WGA, HPA, Ulex europaeus) was sought.The immunohistological observations show that many of the features of a pleomorphic adenoma are constant under the conditions of transplantation. In the transplanted tumour, the same heterogeneity as in the primary tumours can be observed. Autoradiographic studies show little labelling with 3-H thymidine, which is in good accordance with the biological behaviour of the tumour.The distribution of fibronectin shows an interesting association with myoepithelial-like cells.Our results support the hypothesis that the histogenetic origin of the pleomorphic adenoma is a cell pool of the terminal ductal segment. A differentiation towards ductal cells (with production of secretory substances) and towards myoepithelial cells (associated with large amounts of basal membrane like substances) is observed.Supported by the Deutsche Forschungsgemeinschaft and by the Hamburger Stiftung zur Förderung der Krebsbekämpfung     

Oncocytic myoepithelioma and pleomorphic adenoma of the salivary glands

 Twenty oncocytic myoepitheliomas (MEs) and pleomorphic adenomas (PAs) were composed of interlacing fascicles of swollen spindle-shaped or/and epithelioid oncocytic myoepithelial cells showing intense finely granular immunoreactivity with anti-mitochondrial antibody. Focal vacuolation of the cytoplasm of oncocytic myoepithelial cells and their gradual transition into sebaceous metaplasia were observed in 3 cases. Another unusual feature found in 5 cases was the presence of slit-like adenomatoid spaces lined with double-layered oncocytic myoepithelium closely resembling Warthin’s tumour. The nuclei of oncocytic cells were characterized by enlargement, hyperchromasia and polymorphism, which should not be confused with malignancy. Oncocytic change in myoepithelial cells in MEs and PAs can cause pitfalls in the differential diagnosis of salivary gland tumours. We describe some unusual histological features associated with onococytic metaplasia in benign myoepithelial cell-derived salivary gland tumours, hoping to help to avoid the overdiagnosis of malignancy. Received: 24 September 1998 / Accepted: 31 January 1999     

ERBB4/HER4在子痫前期胎盘中的表达

目的探讨子痫前期患者胎盘滋养细胞人表皮生长因子受体4(ERBB4/HER4)的表达及意义。方法采用RT-PCR法检测35例子痫前期患者(子痫前期组)胎盘ERBB4的表达及其与胎盘重量及新生儿出生体重的关系,并与20例正常妊娠妇女(正常妊娠组)比较。结果在子痫前期患者胎盘中,ERBB4 mRNA表达明显高于正常妊娠胎盘,两者有显著性差异(P<0.05)。结论子痫前期患者胎盘ERBB4表达显著增高,与子痫前期的发病密切相关。     

Reconstruction of pleomorphic adenoma of the salivary glands in three-dimensional collagen gel matrix culture

 The morphogenesis of salivary gland pleomorphic adenoma was examined in vitro using three-dimensional (3-D) collagen gel culture. Pleomorphic adenoma cells were isolated from three parotid gland tumours and cultured as monolayers, after which they were subcultured in floating-collagen gel sandwiches. Cells cultured in both conditions were immunohistochemically characterized and compared using antibodies against various proteins representative of each histological component of salivary glands. Monolayers had myoepithelial characteristics, being positive for vimentin and α-smooth muscle actin. In collagen gels, however, the cells assembled in epithelial nests, showing an architecture similar to that of pleomorphic adenoma. The nests were composed of duct-lining epithelial cells that were positive for epithelial markers, surrounded by myoepithelial cells. Collagen gel culture induces multi-directional differentiation of adenoma cells, suggesting that pleomorphic adenomas originate from stem or reserve cells. Received: 26 March 1998 / Accepted: 1 September 1998     

Benign pleomorphic adenoma arising in a parotid lymph node

Summary A rare case of a benign pleomorphic adenoma is reported, arising in a parotid lymph node in a 52-year-old woman. Serial sections showed that the tumor tissue was surrounded by a mantle of lymphoid tissue which had the essential characteristics of a lymph node. The pathogenesis of the lesion is discussed and the literature is briefly reviewed.     

Gene expression and immunolocalization of heparin-binding epidermal growth factor-like growth factor and human epidermal growth factor receptors in human corpus luteum

BACKGROUND: The objective of this study was to elucidate gene expression and immunolocalization of heparin-binding epidermal growth factor-like growth factor (HB-EGF) and human epidermal growth factor receptor (HER) family in the human ovary during luteal growth and regression. METHODS: Ovaries obtained from pre-menopausal women were used for immunohistochemistry and semiquantitative RT-PCR analysis. RESULTS: Immunoreactive HB-EGF was not detected in follicles or oocyte, while HB-EGF became apparent in granulosa luteal cells in the early luteal phase, and most abundant in the mid-luteal phase, but less abundant in the late luteal phase. Immunostaining for HER1 was very weak in granulosa luteal cells in the early and mid-luteal phases, and was not detected in the late luteal phase. Immunoreactive HER4 was abundant in the early luteal phase and became less abundant in the mid-luteal phase, whereas it was negative in the late luteal phase. Semiquantitative RT-PCR analysis revealed that HB-EGF and HER1 mRNA levels were high in the mid-luteal phase, whereas HER4 mRNA expression was high in the early luteal phase. CONCLUSIONS: HB-EGF may play a vital role in regulating luteal growth in a juxtacrine manner and through activating HER4 signalling.     

子痫前期患者胎盘中人表皮生长因子受体1的表达研究

目的通过检测子痫前期患者胎盘滋养细胞人表皮生长因子受体1（ErbB1）的表达情况,探讨胎盘滋养细胞ErbB1表达与子痫前期的关系。方法采用RT-PCR法及免疫组织化学法检测20例正常妊娠妇女（正常妊娠组）与34例子痫前期患者（子痫前期组）胎盘ErbB1的表达。结果在子痫前期患者胎盘中,ErbB1表达明显高于正常妊娠组,两者相比差异有统计学意义（P〈0.05）。结论胎盘中ErbB1表达的升高与子痫前期的发生密切相关。     

Benign metastasizing pleomorphic adenoma of salivary gland: diagnosis of bone lesions by fine-needle aspiration biopsy.

Two cases of benign salivary gland pleomorphic adenomas metastatic to bone (benign-metastasizing pleomorphic adenomas) diagnosed by fine-needle aspiration biopsy are presented. Both primary tumors were slightly atypical cytologically but neither case demonstrated features of carcinoma. The metastatic lesions contained benign epithelial, myoepithelial, and stromal components. In both cases the clinical history was either not known by the radiologist or not communicated to the cytopathologist interpreting the case, and a primary tumor of bone was the leading clinical diagnosis. Obtaining pertinent clinical history and comparing the cytomorphology of the bone aspirate with the primary parotid tumor allowed for an accurate diagnosis in both cases. The differential diagnosis with primary bone tumors is discussed and the importance of clinical history is emphasized.     

Transforming growth factor alpha and epidermal growth factor in human pancreatic cancer.

Overexpression of the epidermal growth factor receptor (EGFR) has been reported as an important molecular abnormality in human pancreatic cancer. There is in vitro evidence that simultaneous overproduction of one of its ligands, transforming growth factor alpha (TGF-alpha), might result in an autocrine loop with an increased proliferation signal. We analysed by immunocytochemical staining a retrospective series of human pancreatic cancers, chronic pancreatitis, and normal fetal and adult pancreatic tissues for the presence of TGF-alpha and epidermal growth factor (EGF). Ductal epithelial cells showed TGF-alpha immunoreactivity in both normal tissue and chronic pancreatitis, and 95 per cent of tumours showed strong immunoreactivity. In contrast, EGF immunoreactivity was not found in normal pancreas, but was expressed in 12 per cent of pancreatic carcinomas. Well-defined areas of EGF immunoreactivity in exocrine ducts showing reactive changes in pancreatitis might represent a benign response to tissue damage similar to that previously described in the gastric mucosa.     

大鼠下颌下腺切除对肝再生的影响

目的：探讨大鼠下颌下腺切除后对肝再生的影响。方法：将21只雄性SD大鼠分成三组：3只正常大鼠作为对照组(N组)；9只行肝大部切除术(H组)；9只行肝大部切除术和双侧下颌下腺切除术(E十H组)。应用增殖细胞核抗原(PCNA)免疫组化和核仁组成区嗜银蛋白(AgNOR)染色方法，对N组，H组，E H组的肝组织进行检测和计量。结果：术后第1天及第3天E H组的PCNA指数、AgNOR数及残余肝脏重量均明显低于H组。结论：结果表明大鼠下颌下腺切除后，肝细胞增殖延迟，肝再行过程延缓，提示下颌下腺分泌的EGF对肝再生起重要调节作用。     

Ultrastructural analysis of salivary gland pleomorphic adenoma, with particular reference to myoepithelial cells

Previous ultrastructural studies of pleomorphic adenoma have presented conflicting results with regard to the role of myoepithelial cells in the histogenesis of this tumour. In the present study specimens of ten major salivary gland pleomorphic adenomas were examined ultrastructurally and a number of cell types identified. The material was subjected to quantification using the stereological method of point counting. The results showed a wide spectrum of differentiation within these tumours in which typical myoepithelial cells were rarely encountered even in situations where they are reported to occur in routine histological preparations. Cells with some myoepithelial features were more numerous but duct cells accounted for the majority of tumour cells. The ultrastructural findings correlated well with previously reported immunocytochemical data and further support certain ideas about salivary gland tumour histogenesis.     

Cyclin D1 and p16 expression in pleomorphic adenoma and carcinoma ex pleomorphic adenoma of the parotid gland

AIMS: To compare cyclin D1 and p16(ink4) (p16) expression in normal tissue, pleomorphic adenoma (PA) and carcinoma ex pleomorphic adenoma (CXPA) of the parotid gland. METHODS AND RESULTS: Immunohistochemistry was used to examine cyclin D1 and p16 expression in 43 parotid tumours (29 PAs and 14 CXPAs). Cyclin D1 and p16 were both significantly more likely to be expressed in the neoplastic than in the normal epithelial and stromal components of PA and CXPA (P < 0.001 and P < 0.005, respectively). Cyclin D1 was more likely to be expressed in the malignant components of CXPA than in the benign components of PA (50% versus 31% and 31%, respectively), but the trend was not statistically significant. There was no evidence of this association for p16 (corresponding positivity rates 69% versus 81% and 52%). CONCLUSIONS: Our findings provide preliminary evidence of roles for cyclin D1 and p16 in the development of PA and for cyclin D1 in the progression of PA to CXPA.