神经生长因子及其受体在前列腺癌中的表达

目的探讨神经生长因子(nerve growth factor,NGF)及其受体TrkA、p75在前列腺增生和前列腺癌中的表达。方法采用免疫组织化学SABC法检测前列腺良性增生10例、高分化8例、中分化14例和低分化23例石蜡包埋组织中NGF和TrkA、p75的表达。结果NGF和TrkA在前列腺增生、高分化癌、中分化癌、低分化癌中的均有表达;而p75在前列腺增生全部表达、高分化癌(8/4)、中分化癌(14/6)、低分化癌(23/3)中的表达呈逐渐降低趋势,其差异有显著性(p<0.05),前列腺增生与高分化癌、中分化癌、低分化癌相比差异均有显著性(p<0.05)。结论NGF和TrkA的表达与前列腺增生和前列腺癌进展无关。p75与前列腺癌恶性进展有关,p75表达减少在前列腺癌过程中起着重要的作用。     

Syndecan-1 expression in thyroid carcinoma: stromal expression followed by epithelial expression is significantly correlated with dedifferentiation

AIM: To investigate the expression of syndecan-1 in thyroid neoplasia. Syndecan-1 is a proteoglycan regulating cell adhesion. Previous studies have demonstrated that decreased expression of syndecan-1 is linked to malignant progression. METHODS AND RESULTS: Syndecan-1 expression in thyroid neoplasia was studied immunohistochemically. Syndecan-1 was expressed in stromal cells as well as neoplastic epithelial cells. Stromal syndecan-1 expression was observed more frequently in papillary carcinomas larger than 10 mm in size than in microcarcinomas and in widely invasive than in minimally invasive follicular carcinomas. Furthermore, poorly differentiated carcinomas showed this phenomenon more than well-differentiated carcinomas, but the expression in undifferentiated carcinomas was similar to that of poorly differentiated carcinomas. Epithelial syndecan-1 expression was more frequently observed in anaplastic (undifferentiated) carcinomas than in papillary and follicular carcinomas. No significant difference in epithelial expression was found between well and poorly differentiated carcinomas, but undifferentiated carcinomas expressed epithelial syndecan-1 more frequently than did poorly differentiated carcinomas. CONCLUSIONS: These results are in contrast to those previously reported for carcinomas at other sites. It is suggested that the role of syndecan-1 in thyroid carcinomas might be unique. Stromal syndecan-1 expression followed by its epithelial expression is significantly related to progression, including dedifferentiation of thyroid carcinoma.     

Oestrogen receptors in benign epithelial lesions and intraduct carcinomas of the breast: an immunohistological study

We examined 198 breast lesions, representing commonly encountered benign epithelial proliferative disorders, lobular carcinoma in situ and intraduct carcinoma, immunohistologically for oestrogen receptors (ER). A mixture of three ER monoclonal antibodies--H222, D75 and D547--was used on sections of routinely processed and paraffin-embedded tissue blocks. Over 65% of the benign and malignant lesions showed some evidence of ER expression and significant staining was recorded by two observers in 28-31% of fibroadenomas, 18-28% of ductal epithelial hyperplasias, 30-40% of sclerosing adenosis cases, 38-45% of papillomas, 60% of in situ lobular carcinomas and 42-45% of intraduct carcinomas. Apocrine metaplastic cells and myoepithelial cells showed absent or only weak staining. Amongst intraduct carcinomas, less than 20% of comedo carcinomas and over 50% of cribriform, papillary and solid variants showed significant ER staining.     

Blood group antigens in vascular tumours

Summary Determination of blood group isoantigens A, B and H, was performed in benign and malignant vascular tumours of the skin and subcutaneous tissue, using the immunoperoxidase technique. No differences were noted between benign haemagioendotheliomas from children or adults: neither tumour showed the presence of antigens in intercapillary cells. Reactive conditions such as angiolymphoid hyperplasia with eosinophilia showed an intense positive reaction to blood group substances of the endothelial proliferative cells. In malignant tumours no relationship between tumour differentiation and loss of blood group isoantigens was seen. Cases of Kaposi's sarcoma did not show antigens in spindle cells or capillaries but in medium sized vessels variable preservation or loss of blood group isoantigens was found.     

Tight junctions in thyroid carcinogenesis: diverse expression of claudin-1, claudin-4, claudin-7 and occludin in thyroid neoplasms.

Claudins and occludin are integral constituents of tight junctions and are deregulated in a variety of malignancies. Their role in thyroid carcinogenesis has not yet been elucidated. This study investigates the expression of occludin and claudin-1, -4 and -7 in thyroid neoplasms. Ninety-one thyroid neoplasms (15 follicular adenomas, 15 follicular carcinomas, 26 papillary carcinomas, 16 papillary microcarcinomas, 8 medullary carcinomas, 3 poorly differentiated carcinomas, 8 undifferentiated carcinomas) were immunostained with antibodies against occludin and claudin-1, -4 and -7. Occludin was mainly expressed in the form of intracytoplasmic vesicles, whereas all claudins tested exhibited membranous immunostaining. Thirteen out of 15 follicular adenomas, 10/15 follicular carcinomas, 24/26 papillary carcinomas, 15/16 papillary microcarcinomas, 1/8 medullary carcinomas, 2/3 poorly differentiated carcinomas and 2/8 undifferentiated carcinomas exhibited claudin-1 expression, whereas claudin-4 was expressed in 13/15, 12/15, 23/26, 13/16, 7/8, 2/3 and 2/8 of the tumors, respectively, and claudin-7 expression was found in 67, 33, 73, 69, 25, 0 and 13% of the cases, respectively. Occludin was expressed in 100% follicular adenomas, 80% follicular carcinomas, 96% papillary carcinomas, 50% papillary microcarcinomas, 50% medullary carcinomas, 33% poorly differentiated carcinomas and 88% undifferentiated carcinomas. Occludin expression was reduced in papillary microcarcinomas, medullary carcinomas and poorly differentiated carcinomas. All claudins exhibited reduced expression in undifferentiated carcinomas. Claudin-1 was additionally reduced in medullary carcinomas and claudin-7 in follicular, medullary and poorly differentiated carcinomas. A correlation between loss of claudin-1 expression and worse disease-free survival was noted on univariate analysis. Dedifferentiation of the thyroid carcinomas is accompanied by reduction in claudin-1, -4 and -7 expression. A differential expression of tight junction proteins in the different histologic types of thyroid gland is noted. Additionally, claudin-1 expression may be an important prognostic indicator of recurrence in thyroid carcinomas.     

Mammary carcinoma arising in microglandular adenosis: a case report

Microglandular adenosis is an uncommon benign breast entity considered as a variant form of adenosis. The diagnosis is frequently made by the pathologist as it is often clinically asymptomatic. Carcinoma arising in microglandular adenosis is very uncommon. We report a case of carcinoma arising in microglandular adenosis in a 54-year-old woman. The immunohistochemical profile, especially S100 protein expression and absence of epithelial membrane antigen, was useful to recognize the microglandular adenosis and the carcinoma of alveolar architecture, while invasion was suggested by the basement membrane disruption highlighted with anti-collagen IV immunostaining. The good prognosis of carcinoma associated with microglandular adenosis points out the importance of distinguishing this lesion from other breast carcinomas.     

The spectrum of morphology in non-neoplastic prostate including cancer mimics

The spectrum of morphology in non-neoplastic prostate includes lesions of prostatic epithelial origin, the most common being atrophy, including partial atrophy, adenosis (atypical adenomatous hyperplasia), basal cell hyperplasia and crowded benign glands, as well as those of non-prostatic origin, such as seminal vesicle epithelium. These lesions often mimic lower-grade prostatic adenocarcinoma whereas others, such as granulomatous prostatitis, for example, are in the differential diagnosis of adenocarcinoma, Gleason grades 4 or 5. Diagnostic awareness of the salient histomorphological and relevant immunohistochemical features of these prostatic pseudoneoplasms is critical to avoid rendering false positive diagnoses of malignancy.     

Monoclonal antibody B72.3 in benign breast lesions.

It has been suggested that the monoclonal antibody B72.3 may be useful as a diagnostic tool in fine needle aspirates of breast masses because it recognises "tumour associated glycoprotein (TAG)-72". The antigen was sought in paraffin wax sections of 43 normal and benign breast biopsy specimens, using the avidin-biotin complex technique, to assess the extent of its presence in non-malignant tissue. Strong focal staining was seen in 21 (49%) cases. In 29 cases of fibrocystic change staining was present in 17 (59%). All areas of apocrine metaplasia were positive, as well as a few normal ducts and acini and occasional areas of adenosis. Focal positivity was present in five out of 12 foci of ductal epithelial hyperplasia and in three out of seven radial scars. Staining was absent in two areas of lobular hyperplasia, three areas of sclerosing adenosis, and in a focus of lactational change. Focal positivity was also seen in two out of five fibroadenomas and in two out of three intraduct papillomas. Five normal subareolar sections and a section of normal lactating breast were negative. It is concluded that B72.3 monoclonal antibody can show focal reactivity with a variety of normal and benign epithelial mammary structures, and it is doubtful that its use would be of any help in differentiating benign from malignant cells in fine needle aspirates.     

Loss of Isoantigens A, B and H in Prostate

Formalin-fixed tissues from 65 prostates were grouped and investigated by the technic of mixed cell agglutination reaction (MCAR) for studying isoantigens A, B and H. The results of this study indicated that the MCAR was strongly positive at the epithelium of the acini in the majority of patients with benign prostatic hyperplasia. On the other hand, patients with primary carcinomas and metastatic carcinomas of prostates were found to be uniformly negative for any agglutination reaction. Prostates from a group of younger individuals only showed a patchy distribution of the MCAR at the epithelium of the acini. In view of these findings, it seemed that the traces of isoantigens in normal prostates show a considerable increase when the disease process of BPH becomes manifest in this organ, while in cases of primary and metastatic carcinomas the isoantigens are totally lost. In the light of previous studies on similar lines, the various possible mechanisms for this sudden transition are discussed.     

Cancer-specific loss of beta-defensin 1 in renal and prostatic carcinomas

In a previous large-scale gene expression profiling study of renal epithelial neoplasms, human beta-defensin-1 (DEFB1) was found to be significantly down-regulated in conventional clear cell (renal) carcinoma. We have now completed an expanded expression analysis of this gene. We performed immunohistochemical analysis for the DEFB1 protein in clinical specimens of both renal cell carcinoma and prostate cancer. In a subset of prostate cancers, we performed laser capture microdissection and RT-PCR to correlate mRNA levels with protein levels. Overall, 82% of prostate cancers exhibit either complete loss of protein expression or only minimal expression, whereas the adjacent benign epithelium retained expression in all cases. Similarly, 90% of renal cell carcinomas show cancer-specific loss of DEFB1 protein. In the prostate cancer subset analysis, mRNA levels correlate with protein levels. We have thus demonstrated the cancer-specific down-regulation of DEFB1 in a large sample of prostatic and renal carcinomas and validated one of the key findings of previous cancer gene profiling studies of prostatic and renal neoplasia.     

Atypical sclerosing adenosis of the prostate: a rare mimic of adenocarcinoma

Cheng L & Bostwick D G
(2010) Histopathology 56 , 627–631 Atypical sclerosing adenosis of the prostate: a rare mimic of adenocarcinoma Aims: Sclerosing adenosis of the prostate is a benign, small, acinar proliferation in dense spindle cell stroma, with a distinct immunohistochemical profiles. It is incidentally found in about 2% of transurethral resection specimens. The aim was to describe cases with significant cytological atypia mimicking cancer, which have not been previously reported. Methods and results: We describe five cases of sclerosing adenosis with significant cytological atypia, referred to as atypical sclerosing adenosis (ASA), which were initially considered suspicious or diagnostic of adenocarcinoma. Seven other cases of typical sclerosing adenosis were used as controls. All cases of typical and atypical sclerosing adenosis displayed an intact basal cell layer, which was immunoreactive for high‐molecular‐weight keratin, S100 protein, smooth muscle actin, and prostate‐specific antigen, with no differences between ASA and the control group. Alpha‐methylacyl‐coenzyme A racemase was negative. Three of four cases of ASA had aneuploid DNA content by digital image analysis. All cases of typical sclerosing adenosis were diploid. During a mean follow‐up of 33 months (range 5–73 months), none developed recurrence or prostatic cancer. Conclusions: ASA is an unusual small, acinar proliferation of the prostate that may be mistaken for adenocarcinoma, and should be distinguished from other mimics, including atypical adenomatous hyperplasia, mesonephric remnant hyperplasia, and post‐atrophic hyperplasia. ASA is a benign lesion and aggressive treatment is unwarranted.     

Cytokeratin immunohistochemistry as a diagnostic tool for distinguishing malignant from benign epithelial lesions of the prostate.

The basal cell layer (BCL) is believed to be absent in malignant but present in nonmalignant epithelial lesions of the prostate. Using the avidin-biotin-peroxidase complex (ABC) immunoperoxidase method, we examined the value of the monoclonal antibody cocktail MA-903, which stains selectively the prostatic BCL layer, in the distinction between benign and malignant epithelial lesions of the prostate. We immunostained histologic sections of 63 prostates, containing 235 morphologic appearances: normal prostate glands, 43; benign prostate hyperplasia (BPH), 59; basal cell hyperplasia (BCH), 24; adenosis, seven; prostatic intraductal neoplasia (PIN 1), 21; PIN 2, 25; PIN 3, 16; and cancer, 40. Some degree (continuous, continuous with focal disruption, and disrupted patterns) of basal cell staining was demonstrable in all normal and BPH, BCH, and PIN 1 lesions, but was absent in 39 of 40 cancers. However, not every gland in benign lesions stained positively. Further, two of 25 PIN 2 and six of 16 PIN 3 lesions failed to reveal BCL. Our results suggest that the presence or absence of BCL, predicated on cytokeratin MA-903 immunoreactivity, may be a useful indicator in the distinction between benign and malignant epithelial lesions of the prostate.     

Mammaglobin expression in gynecologic malignancies and malignant effusions detected by nested reverse transcriptase-polymerase chain reaction

The detection of micrometastatic disease remains a challenge for the diagnosis and monitoring of malignant disease. RT-PCR for human mammaglobin (hMAM) was recently shown to provide a sensitive method for assessing circulating breast cancer cells in peripheral blood. This study was aimed at investigating hMAM expression in normal and malignant tissue from the female genital tract and the prostate as well as in malignant effusions derived from gynecologic malignancies. hMAM expression was analyzed with nested RT-PCR in 152 samples of normal (n = 73) and malignant epithelial tissues (n = 79) and in 33 specimens of various normal mesenchymal tissue types. We found hMAM expression was not restricted to the normal mammary gland and breast carcinoma but was also detectable in most specimens of benign and malignant epithelial tissue from the ovary (97% versus 95%), uterus (both 100%), and cervix (91% versus 90%). Notably, hMAM expression was also found in benign prostatic hyperplasia (45%) and in prostate cancer (55%). A much lower expression rate was found in various normal and benign mesenchymal tissues (12%). In keeping with our previous data, hMAM expression was absent in all control samples (n = 124) of peripheral blood and bone marrow from healthy volunteers and patients with hematologic malignancies. In pleural or peritoneal effusions (n = 42) from patients with carcinomas of the breast, endometrium, or ovary, hMAM positivity was noticed in the majority of cases (74%), whereas only 52% of the specimens were cytologically positive for tumor cells. In conclusion, hMAM expression assessed by nested RT-PCR is a sensitive molecular marker for detecting micrometastatic tumor spread into pleural effusions and ascites from patients with breast cancer and various other gynecologic neoplasms.     

Expression of prolactin receptors in normal, benign, and malignant breast tissue: an immunohistological study

AIMS: Prolactin plays an important role in the proliferation and differentiation of normal breast epithelium, and possibly in the development of breast carcinoma. The effects of prolactin are mediated by its receptor; thus, alteration in the expression of this receptor could be important in studying the biology of breast cancer. This investigation was aimed at comparing the expression of prolactin receptors in normal, benign, and malignant breast tissue. MATERIAL/METHODS: The expression of prolactin receptors was studied in paraffin wax embedded sections of 102 breast biopsies (93 female and nine male), using the monoclonal antibody B6.2, and the avidin-biotin immunoperoxidase technique. Six biopsies were normal, 34 had benign lesions, and 62 were malignant. RESULTS: In normal cases, prolactin receptor positivity was seen only on the luminal borders of the epithelial cells lining ducts and acini. In most benign lesions, variable degrees of luminal and cytoplasmic staining were seen. Cells showing apocrine metaplasia and florid regular ductal epithelial hyperplasia were mostly negative. In malignant cases, the staining pattern was mostly cytoplasmic and heterogeneous. Forty one of the 59 carcinomas in women showed a degree of positivity involving 10-100% of the tumour cells. A significant direct correlation was found between prolactin receptor and oestrogen receptor staining when only cases that scored more than 100/300 for the latter receptor, using the H scoring system, were considered (p = 0.0207). No correlation was found between prolactin receptors and progesterone receptors, patient's age, tumour size, tumour grade, or axillary lymph node status. CONCLUSIONS: Prolactin receptors seem to be expressed at different cellular sites in normal, benign, and malignant breast epithelial cells. The receptor is expressed in more than two thirds of female breast carcinomas, suggesting that it may play a role in the pathogenesis of the disease. The positivity is correlated with moderate and strong staining for oestrogen receptors in tissue sections, but not with other prognostic factors.     

胎肺及肺癌花生凝集素受体的观察

应用生物素化花生凝集素(PNA)对胎肺及45例肺癌进行组织化学研究.结果显示:胎肺内支气管上皮顶部胞膜及胞质呈PNA阳性.肺鳞癌及肺腺癌PNA受体增多,且分布失去极性.本文提示PNA受体改变可作为内胚层肿瘤的标志之一,尤其对腺癌有相对特异性.PNA受体在胚胎及肺癌均表达可能提示PNA是一种癌胚抗原.     

Myoepithelial cells in the differential diagnosis of complex benign and malignant breast lesions: an immunohistochemical study.

The distinction between sclerosing adenosis, radial scars, noninvasive carcinomas occurring in sclerosing adenosis, and invasive carcinoma can be difficult. The identification of a myoepithelial (ME) cell layer is helpful in establishing a diagnosis of complex benign breast proliferation as well as intraepithelial neoplasia in sclerosing adenosis. We reviewed pathologic material from patients with tubular carcinoma (23) and complex breast proliferations (28), including sclerosing adenosis (12), radial scars (9), sclerosing adenosis with intraepithelial neoplasia (5), and sclerosing adenosis with atypical apocrine metaplasia (2). Immunoperoxidase stains on formalin-fixed, paraffin-embedded tissue using a muscle actin-specific antibody of clone HHF35 and high molecular weight cytokeratin of clone 34 beta E12 (HMW keratin) were performed to identify myoepithelial cells. Muscle actin was uniformly reliable in staining ME cells, as well as other actin-containing cells such as myofibroblasts and vascular smooth muscle. HMW keratin was less reliable, being poorly sensitive and less specific than muscle actin for labeling of ME cells. ME cells were readily identified at the periphery of ductules in all complex benign breast lesions. The presence of ME cells distinguished intraepithelial neoplasia involving sclerosing adenosis from invasive carcinomas. Well differentiated invasive carcinoma forming tubular structures lacked a ME cell layer.     

Expression of blood group antigens by normal bronchopulmonary tissues and common forms of pulmonary carcinomas.

The expression of ABH and Lewis antigens has been studied in a series of pulmonary carcinomas, in areas of squamous metaplasia, and in normal adjacent bronchopulmonary tissues by means of a panel of lectins and monoclonal antibodies. All respiratory epithelial cells can express antigens, with the exception of glandular serous cells. The expression of AB antigens is rather homogeneous, while Lewis antigens are expressed in a more irregular pattern, alternating positively stained cells with negatively stained cells in the same microscopic field. The expression of blood group antigens allows the identification of residual pneumocytes inside the tumor and the proper classification of some neoplasms. Metaplastic areas show a variation in the staining profile when compared with normal tissues and pulmonary carcinomas. The most significant findings are the deletion of A antigen and the strong expression of Le antigen. Pulmonary carcinomas are composed by a heterogeneous population and tend to express antigens in the more differentiated cases or areas. The most important findings are the deletion of AB antigens and the strong expression of Le(y) antigen.