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1.
AIMS: To characterize the cellular component in pleomorphic adenoma (PA) that undergoes malignant transformation in carcinoma ex pleomorphic adenoma (CXPA). METHODS AND RESULTS: A panel of antibodies against cytoskeletal proteins was applied in 16 cases of CXPA: intracapsular carcinoma (five cases), minimally invasive (four cases) and frankly invasive (seven cases). The CXPAs were classified into two main groups according to their predominant cellular component as detected by the panel of antibodies: (i) carcinomas with only epithelial differentiation (75% of the cases), and (ii) carcinomas with a myoepithelial component (25%). CXPA with only epithelial differentiation showed two types of malignant areas in the part of the tumour that was confined by the PA capsule: (i) intraductal carcinoma areas characterized by ductal structures containing both benign myoepithelial cells positive for alpha-smooth muscle actin (alpha-SMA), vimentin and cytokeratin (CK)14 and proliferating atypical luminal cells reactive for CK7, CK8 and CK19, and (ii) carcinoma areas composed only of epithelial cells reactive for CK7, CK8 and CK19. In the latter, the cells presented morphological and immunohistochemical characteristics similar to those found in areas of invasive carcinoma outside the PA capsule. CXPAs with a myoepithelial component were composed mainly or exclusively of cells that expressed vimentin and alpha-SMA. In this group, ductal structures reminiscent of PA filled by malignant cells were not identified. CONCLUSION: Most CXPAs consist only of epithelial cells that have an immunoprofile comparable to ductal luminal cells of PA. These malignant luminal cells arise in the duct-like structures as intraductal carcinoma and probably only at this early stage of development should the lesion be considered as a non-invasive carcinoma.  相似文献   

2.
BACKGROUND AND AIMS: Endothelin-1 expression is increased in infiltrating duct carcinoma and is associated with larger tumour size, higher histological grade and lymphovascular permeation. This has not been evaluated in phyllodes tumours, which are uncommon fibroepithelial lesions with potential for local recurrences or distant metastasis. While the grading of phyllodes tumours depends on a combination of histological parameters, prediction of their behaviour remains difficult. METHOD: A large series of 461 phyllodes tumours (291 benign, 115 borderline malignant and 55 frankly malignant) were evaluated for endothelin-1 expression in both the epithelial cells and stromal cells by immunohistochemistry; results were correlated with the tumour grade. RESULTS: For benign phyllodes tumours, the epithelial staining of endothelin was negative, weak, moderate and strong in 6%, 26%, 15% and 53% of cases respectively; results were 4%, 18%, 19% and 59% respectively for borderline and 6%, 18%, 6% and 70% respectively for frankly malignant tumours. For the stromal staining, the negative, weak, moderate and strong staining was 32%, 19%, 18% and 31% respectively for benign phyllodes, 24%, 13%, 10% and 53% respectively for borderline and 8%, 16%, 17% and 59% respectively for frankly malignant tumours. There was correlation between epithelial and stromal staining, and the stromal staining correlated with histological features of stromal cellularity, stromal cell nuclear pleomorphism, margin status and stromal overgrowth. CONCLUSION: These observations suggest a close relationship between the epithelial and stromal elements in phyllodes tumours; endothelin may play a significant role in the malignant progression of phyllodes tumours.  相似文献   

3.
Malignant phyllodes tumor of the breast is a rare biphasic neoplasm, the stromal component of which may show homologous and heterologous sarcomatous elements. We present a case of a histologically malignant phyllodes tumor with sarcomatous overgrowth, affecting a 37-year-old woman in whom a chondrosarcomatous component constituted over 80% of the tumor volume. A malignant phyllodes tumor displaying a predominant chondrosarcomatous component is indeed rare, and the differential diagnosis could well affect the therapeutic approach, mainly with regard to metaplastic carcinoma and primary chondrosarcoma of the mammary gland. Thus, it is important to sample the tumor thoroughly to detect the presence of any area of typical phyllodes tumor, which could be very small. Immunohistochemical stains also should be performed so as to exclude a malignant epithelial component. After the final morphological diagnosis, our patient underwent a complete mastectomy without axillary disection. One year later, no local recurrence or metastasis was apparent.  相似文献   

4.
The correlation between the histology and biologic behavior of phyllodes tumor was studied in order to establish the histologic criteria of this tumor, particularly its malignant counterpart. A preliminary analysis of five tumors with metastases revealed that a single essential indicator of malignant potential was the presence of a disproportionate overgrowth of the stromal elements at the expense of the ductal element. The presence or absence of such stromal overgrowth in the tumor showed a positive correlation with the degree of stromal atypism and the rate of mitoses. Seventeen out of 45 tumors were determined to be malignant, on the basis of our criteria. The arrangement of the stromal component in malignant phyllodes tumors was usually one of the particular sarcomatous types, with or without the focal areas of one of the specified types of sarcoma. On the other hand, 24 tumors recurred locally but never metastasized, and were preferentially interpreted to be benign phyllodes tumor. Histologically, these tumors had a general architecture resembling that of fibroadenoma but were characterized by high cellularity expressed by the distinct formation of bundles or fascicles of stromal tumor cells. The remaining four tumors seemed to form a borderline phyllodes tumor subset. A follow-up study revealed that, irrespective of the mode of therapy, the outcome of patients with phyllodes tumor was well correlated with the histologic criteria we proposed. ACTA PATHOL JPN 38: 21–33, 1988.  相似文献   

5.
AIMS: The tumour suppressor gene maspin is reported to inhibit the motility, invasiveness and metastasis of breast cancer cells. Maspin is expressed in normal mammary myoepithelial cells but is down-regulated during the progression of ductal carcinoma. However, we recently reported that maspin expression was frequently observed in invasive ductal carcinoma (IDC) with an aggressive phenotype, and it was a strong indicator of a poor prognosis. To our knowledge, to date, there has been no report investigating maspin expression in a large series of ductal carcinoma in situ (DCIS). METHODS AND RESULTS: To clarify whether there is down-regulation during the progression of ductal carcinoma, we immunohistochemically investigated the expression of maspin in 145 DCIS, 92 invasive ductal carcinomas with a predominant intraductal component as well as 94 usual ductal hyperplasias and 27 atypical ductal hyperplasias. The expression of maspin in carcinoma cells was observed in 9.6% (14 of 145) of DCIS and 18.5% (17 of 92) of IDC with a predominant intraductal components. It significantly correlated with larger tumour size (P = 0.013; P = 0.042), higher histological grade (P = 0.015; P = 0.0003) and the presence of comedo-necrosis (P = 0.000005; P = 0.0074) in DCIS and IDC with a predominant intraductal components, respectively. In epithelial cells, the expression of maspin was observed in only one case of usual ductal hyperplasia, and all cases of atypical ductal hyperplasia were negative. CONCLUSIONS: These results and our previous investigation in which 27.4% of IDC were positive for maspin suggest that the expression of maspin in epithelial cells could be up-regulated during the progression of ductal carcinoma, and that it could be correlated with the acquisition of an aggressive phenotype.  相似文献   

6.
The purpose of this study is to evaluate cytologically two cases of mammary fibromatosis (MF). Prior to FNAC, clinical and mammographic suspicion of carcinoma and fibroadenoma were present. In both cases cytology disclosed the presence of numerous spindle cells admixed with epithelial cells. In the first case, carcinoma was excluded and the diagnosis of “spindle-cell proliferative lesion” was established. The second case was erroneously diagnosed as “cellular fibroadenoma” due to the presence of monolayered ductal epithelial groups and stromal tissue. In both cases local excision of the lesion was recommended. Although in a strict sense fibromatosis is a pure stromal lesion, the frequent presence of epithelial groups in the smears should raise a differential diagnosis with other more frequent mixed (epithelial and stromal) lesions such as fibroadenoma, cystosarcoma phyllodes, and metaplastic carcinoma. Due to the fact that clinically and mamographically MF is frequently confused with malignancy, preoperative recognition is essential since in many cases it would avoid unnecessary radical surgery. In this sense cytology offers very important preoperative information. Diagn. Cytopathol. 1997;17:363–368. © 1997 Wiley-Liss, Inc.  相似文献   

7.
The correlation between the histology and biologic behavior of phyllodes tumor was studied in order to establish the histologic criteria of this tumor, particularly its malignant counterpart. A preliminary analysis of five tumors with metastases revealed that a single essential indicator of malignant potential was the presence of a disproportionate overgrowth of the stromal elements at the expense of the ductal element. The presence or absence of such stromal overgrowth in the tumor showed a positive correlation with the degree of stromal atypism and the rate of mitoses. Seventeen out of 45 tumors were determined to be malignant, on the basis of our criteria. The arrangement of the stromal component in malignant phyllodes tumors was usually one of the particular sarcomatous types, with or without the focal areas of one of the specified types of sarcoma. On the other hand, 24 tumors recurred locally but never metastasized, and were preferentially interpreted to be benign phyllodes tumor. Histologically, these tumors had a general architecture resembling that of fibroadenoma but were characterized by high cellularity expressed by the distinct formation of bundles or fascicles of stromal tumor cells. The remaining four tumors seemed to form a borderline phyllodes tumor subset. A follow-up study revealed that, irrespective of the mode of therapy, the outcome of patients with phyllodes tumor was well correlated with the histologic criteria we proposed.  相似文献   

8.
The DNA content of the various neoplastic elements of 12 Feulgen-stained metaplastic breast carcinomas was measured by image analysis. Spindle cell, osseous, chondroid, rhabdomyoid, or squamous cell metaplastic elements comprised at least half of each neoplasm in which an invasive ductal carcinoma component also was identified. The epithelial elements in all of the neoplasms were aneuploid, as was the metaplastic component in 11 of the cases. Multiple stem cell lines were detected in the ductal carcinoma component in 4 cases and in the metaplastic components in 5 cases. Our findings lend support to the view that metaplastic elements are derived from malignant epithelial cells, rather than from benign stromal cells. Neither aneuploidy nor the presence of multiple stem cell lines was a useful predictor of the biologic behavior of these 12 neoplasms.  相似文献   

9.
Malignant phyllode tumor is a rare biphasic breast tumor consisting of a malignant mesenchymal component and an epithelial component that is usually benign. We report an unusual case of a malignant phyllode tumor of the breast with neoplastic features of both the epithelial and stromal components. The patient was a 39-year-old woman with family history for breast carcinoma. Grossly, the excised tumor was a 9 x 7 x 5.5 cm gray lobulated mass with infiltrative margins and necrotic-hemorrhagic areas. Histologically the tumor consisted mainly of neoplastic mesenchyme with non invasive comedo, cribriform and micropapillary features of the ducts. Three months after the excision of the neoplastic mass, the patient developed an infiltrating ductal carcinoma of the opposite breast. Hereditary and bilateral tumors are commonly associated with germline mutations. Tissue from both neoplasms however did not express either BRCA1 or BRCA2 mutations.  相似文献   

10.
Malignant phyllodes tumors of the breast are rare biphasic neoplasms, the stromal component of which may show homologous and heterologous sarcomatous elements. Malignant epithelial transformation is rare. It has been reported in a few cases of in situ and infiltrating ductal or lobular carcinoma. Rarely, breast carcinomas and phyllodes tumors may also develop in the same breast independent of each other. To our knowledge, this is the first case of two different types of tumor occurring in the same breast at the same time in a post-osteosarcoma case.  相似文献   

11.
Malignant phyllodes tumor is a rare breast tumor with neoplastic epithelial and stromal components. The stromal component may show homologous and heterologous sarcomatous elements, including chondrosarcomatous and osteosarcomatous differentiation. Because these tumors may present with an almost exclusively sarcomatous component, it is important for the pathologist to include this entity in the diagnostic considerations of fine-needle aspirations of breast neoplasms showing sarcomatous differentiation. Following surgical excision, careful examination of the gross specimen and thorough sampling of the specimen is recommended before rendering a definitive histologic diagnosis. We describe the cytologic and histologic findings in a case of malignant phyllodes tumor with sarcomatous overgrowth showing predominantly chondrosarcomatous differentiation.  相似文献   

12.
Vimentin expression in benign and malignant breast epithelium.   总被引:1,自引:0,他引:1       下载免费PDF全文
AIMS--To determine vimentin expression in epithelial cells in benign breast disease and malignant breast tumours; to assess the value of vimentin expression as a prognostic indicator in breast carcinoma. METHODS--Frozen and formalin fixed, paraffin wax embedded sections from 78 carcinomas, three phyllodes tumours, 19 fibroadenomas and 19 cases of fibrocystic disease were examined with a monoclonal antibody from the V9 clone. A correlation between vimentin expression and known prognostic indicators was sought in ductal carcinomas. The intracellular localisation of vimentin was examined in benign and malignant lesions. RESULTS--Vimentin expression was identified on frozen section in the cells of ductal (53%), lobular (86%), and mucinous (33%) carcinomas and in the luminal epithelium of fibroadenomas (68%), cases of fibrocystic disease (47%), and a malignant phyllodes tumour. Formalin fixation reduced the percentage of carcinomas and cases of benign disease in which vimentin was detected. This reduction was more pronounced in fibroadenoma and fibrocystic disease than in ductal carcinoma. Associations were identified between vimentin expression as detected on frozen section and tumour grade, size, number of lymph nodes affected, oestrogen receptor content and growth fraction. Only the association with grade was significant (p = 0.045). There was no significant correlation between any of these prognostic variables and vimentin expression on paraffin wax sections. There was no difference in the intracellular localisation of vimentin staining between benign and malignant lesions, or between low and high grade ductal carcinomas. CONCLUSION--There is some loss of vimentin immunoreactivity after formalin fixation. Vimentin expression does not assist in differentiating between benign and malignant breast disease, but is correlated with tumour grade in ductal carcinoma.  相似文献   

13.
Fibroadenoma and phyllodes tumour of the breast are both fibroepithelial tumours. Although progression to epithelial malignancy has been described, the behaviour of most fibroadenomas is benign. Phyllodes tumours, on the other hand, can display locally destructive growth and can even metastasize. A relationship between the two tumours has been suggested in the literature. This study investigated the clonality of both the stroma and the epithelium of these fibroepithelial tumours and attempted to construct a model in which fibroadenoma can progress in both an epithelial and a stromal direction. Fibroadenomas (n=25) and phyllodes tumours (n=12) were selected for analysis. Tissue was microdissected and analysed for clonality using a polymerase chain reaction (PCR)-based assay targeted at an X-linked polymorphic marker, the human androgen receptor gene (HUMARA). Nineteen fibroadenomas and nine phyllodes tumours could be analysed. Normal-appearing epithelium, hyperplastic epithelium, and stroma removed from fibroadenomas were polyclonal. As expected, carcinoma in situ (CIS) removed from four fibroadenomas was monoclonal. Three areas of apparent stromal expansion within fibroadenoma were monoclonal, suggesting stromal progression. Mostly, the stroma of phyllodes tumours was monoclonal and the epithelium polyclonal. In two cases, however, the epithelium seemed to be monoclonal, whereas in three other cases the stromal component was polyclonal. These findings indicate that fibroadenoma can progress in an epithelial direction to CIS and in a stromal direction to phyllodes tumour.  相似文献   

14.
AIMS: Tumour vascularity is considered a prognostic indicator in breast carcinoma, but its utility in mammary phyllodes tumour has not been explored. The authors report the correlation between intratumoral microvessel density and the histological grade of phyllodes tumour. METHODS AND RESULTS: Forty cases of phyllodes tumour were reviewed for stromal cellularity, overgrowth, cytological pleomorphism, mitotic count and margin pattern. Using established criteria, these were diagnosed as benign (n=28), borderline (n=10) and malignant (n=2). Microvessel density was counted on CD31-stained slides as the number of vessels per high power field. For benign phyllodes tumour, the range was 7-26.2 (mean 13.1); for borderline phyllodes tumour the range was 17.2-32.5 (mean 22.4); for malignant phyllodes tumour the range was 25.9-33.3 (mean 29.6). The difference between the benign and borderline groups was significant (P < 0.0001) but that between the borderline and malignant groups was not, due to the small number of malignant cases. CONCLUSIONS: There is a significant difference in stromal microvessel density between benign and borderline phyllodes tumour. Although the small number of cases of malignant phyllodes tumour limits further interpretation, we believe that microvessel density can be used as an additional objective histological parameter in the evaluation of phyllodes tumour.  相似文献   

15.
In a previous study of phyllodes tumours, it has been shown that both the stroma and the epithelium can exhibit distinct molecular changes, suggesting that both are part of the neoplastic process. In view of this finding, it was decided to study stromal-epithelial interactions in these tumours by examining the Wnt-APC-beta-catenin pathway. Beta-catenin and cyclin D1 immunohistochemistry was performed on 119 phyllodes tumours. Eighty-six (72%) showed stromal nuclear beta-catenin localization and in 57% the staining was moderate or strong; however, of the eight malignant tumours in the series, seven showed absent or weak nuclear staining (p<0.025). In no tumour was nuclear beta-catenin staining seen in the epithelial component. Moderate or strong stromal cyclin D1 staining correlated with nuclear stromal beta-catenin staining (p<0.05). Forty-five of the tumours, including two malignant lesions, were screened for beta-catenin exon 3 mutations using SSCP and sequencing, but none was found. Loss of heterozygosity (LOH) of the marker D5S346 was used to infer APC mutation, but only one (benign) tumour showed LOH. Wnt2 and Wnt5a mRNA was localized by in situ hybridization in 13 cases (three malignant) chosen to reflect the different beta-catenin staining patterns. There was an association between strong nuclear beta-catenin staining of stromal cells and epithelial Wnt5a expression (p<0.0015). These data suggest that stromal proliferation in benign phyllodes tumours relies on abnormalities in the Wnt pathway which result not from mutation, but from Wnt5a expression in the epithelium. In the progression to malignancy, the stromal proliferation appears to become independent of the Wnt pathway and, presumably, of the epithelial component of these tumours.  相似文献   

16.
The stroma of fibroadenoma and phyllodes tumor usually consists of fibroblastic proliferation. Rarely the stroma contains bundles of smooth muscle. Pseudoangiomatous hyperplasia of the mammary stroma has been described in fibroadenomas. However, true benign vascular stroma has not been reported. We report a case of a 34-year-old Chinese woman who presented with a large mass occupying the entire left breast. Left mastectomy was performed and showed a large, well-circumscribed, lobulated, rubbery-firm tumor measuring 13 x 10 x 6 cm. Microscopic examination revealed a fibroepithelial tumor formed by an organoid pattern of ductal structures with a very striking stromal appearance composed of extensive vascular proliferation and that demonstrated strong immunoreactivity for CD31, CD34, and Factor VIII. Ultrastructural examination revealed intercellular junctions, basal lamina, pinocytotic vesicles, and Weibel-Palade bodies in the cells lining the vascular spaces, confirming their endothelial nature. These findings rule out the diagnosis of pseudoangiomatous hyperplasia. The patient developed local recurrence a year later, and the resection showed malignant phyllodes tumor with ductal carcinoma in situ.The extensive vascular stroma noted in the primary tumor may have played a role in the malignant transformation of the epithelial and stromal components in this tumor.  相似文献   

17.
BACKGROUND: The interaction between transmembrane receptors on epithelial tumor cells and the surrounding extracellular matrix molecules is important in tumor progression and metastasis. This interaction is best exemplified by the relationship of the receptor CD44 and the extracellular matrix component hyaluronan (HA). This study seeks to evaluate the expression and the correlation of CD44s, CD44v6, and HA in normal, hyperplastic, and malignant breast epithelium and stroma. MATERIALS AND METHODS: Archival paraffin-embedded tissue from cases of normal breast tissue (n=10), intraductal hyperplasia without atypia (n=13), ductal carcinoma in situ (DCIS) (n=24), stage I infiltrating ductal carcinoma (n=28), stage II infiltrating ductal carcinoma (n=31), and their corresponding positive lymph nodes were retrieved from the surgical pathology files. Tissue sections were evaluated for the expression of CD44s, CD44v6, and HA in the epithelial and stromal cells by immunohistochemistry. RESULTS: Ductal epithelial cells and myoepithelial cells expressed CD44s in all cases of normal and benign breast tissue. The expression of CD44s in breast epithelium progressively decreased with increasing deviation from normal histology: 83% in DCIS, 46% in stage I ductal carcinoma and 26% in stage II ductal carcinoma. The reverse trend was observed for CD44v6 in ductal epithelium: 0% in normal breast, 15% in intraductal hyperplasia, 100% in DCIS, 82% in stage I infiltrating ductal carcinoma, 94% in stage II carcinoma, and 100% of metastatic carcinoma in the lymph nodes. HA was noted exclusively in the stroma but not in the epithelial cells. HA was faintly expressed in the intralobular stroma of normal breast tissue, confined to a narrow faint band adjacent to intraductal hyperplasia and localized to a broad well-defined band around DCIS. Stromal HA staining was more diffuse and intense in infiltrating carcinomas and was particularly pronounced surrounding the metastatic deposits in lymph nodes. CONCLUSIONS: This study demonstrates decreased expression of CD44s accompanied by increased expression of CD44v6 and increased stromal HA in breast cancer. These findings suggest that CD44s, CD44v6, and HA play complementary roles in the development and progression of breast cancer.  相似文献   

18.
W Q Zheng  L M Looi  P L Cheah 《Pathology》1999,31(3):247-251
In the metastatic process, proteolytic enzymes play an important role in mediating the passage of cancer cells through the basement membrane and extracellular matrix. We have compared cathepsin-D (CD) expression in a range of benign and malignant breast lesions so as to investigate its role in breast cancer progression. One hundred and sixty-two breast samples, comprising 18 fibroadenomas, 22 fibrocystic disease, 96 invasive ductal carcinoma and 26 lesions with intraductal carcinoma components, were evaluated for CD expression by the standard avidin-biotin-immunoperoxidase complex method on formalin-fixed, paraffin-embedded histological sections using a commercial antibody against human cathepsin-D. Of the invasive ductal carcinomas, 61.5% showed stromal cell CD positivity, whereas 48.9% expressed CD positivity in neoplastic cells. There was significant correlation between neoplastic cell and stromal CD positivity. The prevalences of CD positivity in both neoplastic and stromal cell components were significantly higher (P < 0.05 and P < 0.01, respectively) in histological grade III tumors compared to grades I and II carcinomas. CD expression by either neoplastic or stromal cells did not show significant correlation with patient age and tumor size. Only 15% of intraductal carcinomas were CD positive and expression was limited to neoplastic cells. Neither epithelial nor stromal cells in fibrocystic lesions and fibroadenomas were CD positive, but a weak to moderate positivity was observed within myoepithelial cells in mammary ducts. These findings provide insights into the mechanism whereby tumors with high histological grade mediate invasion into tissue. The role of stromal cells in tumor progression and the means of their recruitment deserve further study.  相似文献   

19.
One hundred and ninety patients with mammary ductal carcinoma were studied to evaluate the correlation of proportions of intraductal and invasive tumor growth to histologic and immunohistochemical features. Initially, attempts were made to divide the cases into 6 groups according to the proportion of extraductal invasive areas within the whole tumor. It has been found that ductal carcinoma could be divided, on this criterion, into 2 groups. One comprised tumors in which invasive areas made up less than 20% of the tumor, the other included those with invasive areas exceeding 20%. In the former, intraductal and invasive components exhibited a lower grade of nuclear and tumor component and a higher incidence of cells with CEA immune positivity. The latter manifested higher grades in both intraductal and invasive components and a lower incidence of CEA positive cells. Many of the latter tumors had a solid or comedo-like growing pattern of the intraductal component. There was a significant difference in the prognosis between the two categories. We conclude that like intraductal carcinomas, invasive ductal carcinomas with a predominant intraductal component should be considered a lower grade malignancy.  相似文献   

20.
目的 探讨CD10免疫标记乳腺肌上皮细胞的可行性。方法 收集50例乳腺良恶性病变的石蜡包埋标本(腺瘤、纤维腺瘤、叶状肿瘤、纤维囊性病、导管内乳头状瘤、乳头腺瘤、导管内癌、小叶内癌、浸润性导管癌、浸润性小叶癌),采用免疫组化(S-P法)检测CD10在上述病变中的表达。结果 在乳腺良性病变中,CD10阳性的肌上皮细胞连续地环绕在普通型增生的小导管的周围。但在囊性扩张或不典型上皮增生的导管周围,CD10阳性细胞不连续,甚至不见阳性细胞。导管原位癌的癌细胞巢外周的阳性细胞由完整到不完整,甚至完全缺失。在浸润性癌中癌巢周围不见阳性细胞,在早期浸润性癌中可见残存的阳性细胞。除少许癌细胞和肌纤维母细胞表达CD10外,其余癌细胞、肌纤维母细胞、血管平滑肌细胞和上皮细胞均不表达CD10。结论 CD10标记肌上皮细胞具有较高的敏感性和特异性,可以作为肌上皮细胞的有效标记物。  相似文献   

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