Heat shock protein 27 is associated with decreased survival in node-negative breast cancer patients.

BACKGROUND: Heat shock protein 27 (hsp27) is a molecular chaperone which supports cells to keep their homeostasis under stressful conditions. It is associated with resistance to chemotherapeutics, radiation and hyperthermia. The aim of this retrospective study was to investigate the prognostic value of hsp27 for patients with node-negative breast cancer. MATERIALS AND METHODS: Paraffin sections of 191 patients were stained immunohistochemically with a monoclonal antibody against hsp27. Median follow-up was 177 months. The results were correlated with clinical and histopathological parameters using the Chi-square test. RESULTS: There was no significant correlation between hsp27 expression and standard histopathological features or the proliferation marker ki-67. Disease-free survival (DFS) was not altered for patients expressing hsp27-positive tumors, whereas overall survival (OS) [p=0. 02] and survival after first recurrence (SR) [p=0.01] were significantly decreased. CONCLUSION: The expression of hsp27 in primary breast cancers is associated with a short survival for node-negative patients.

PTEN mutations do not cause nuclear beta-catenin accumulation in endometrial carcinomas.

PTEN: and beta-catenin mutations constitute the predominant genetic alterations in endometrioid carcinomas of the endometrium. PTEN encodes a dual-specificity phosphatase with lipid phosphatase and protein tyrosine phosphatase activities that regulate both apoptosis and interactions with the extracellular matrix. Recent studies have associated PTEN mutations with tumorigenesis of prostate carcinoma via the Wnt signaling pathway, leading to nuclear beta-catenin accumulation. To elucidate the potential interaction of PTEN and beta-catenin in endometrial cancer, we performed mutation analyses of the entire PTEN gene and of exon 3 of the beta-catenin gene that is most frequently targeted by mutations. A total of 82 endometrial carcinomas comprising 62 type I endometrioid carcinomas and 20 type II high-grade carcinomas were investigated. In addition in a subset of 22 carcinomas, the intracellular beta-catenin distribution was analyzed by immunohistochemistry. Overall, 20 (24.4%) of 82 tumors revealed mutations in the PTEN gene, and 16 (19.5%) of 82, in the beta-catenin gene. Six tumors (7.3%) showed mutations in both the PTEN and beta-catenin gene. Mutations were mainly detected in endometrioid carcinomas of the endometrium. As expected, a striking nuclear accumulation of beta-catenin could be shown in tumors with beta-catenin mutations. In the vast majority of tumors with PTEN mutations, a regular staining pattern of the cytoplasmic and membranous compartments was found. We therefore conclude that, in contrast to prostate cancer, mutations in the PTEN gene seem not to affect cellular distribution of the beta-catenin protein in endometrial carcinomas.

Endometrial carcinoma recurrence in an abdominal scar 14 years after total hysterectomy.

BACKGROUND: Abdominal scar recurrence of endometrial carcinoma after hysterectomy has been only occasionally described and occurred mostly within 5 years after surgery. Direct tumor cell seeding in the abdominal wound at the time of operation is thought to be most likely the cause of recurrence. CASE: The patient underwent total abdominal hysterectomy for early stage endometrial carcinoma. She presented 14 years later with an abdominal scar recurrence that was radically resected. Histology of the tumor was similar to that of the primary carcinoma. CONCLUSION: Recurrences of endometrial carcinoma in an abdominal scar can occur even many years after hysterectomy and the concept of dormant cancer tumor cells is discussed as cause of recurrence rather than direct tumor cell implantation at the time of operation.

[Isolated Rosai-Dorfman disease]. / Isoliert extranodale Rosai-Dorfman-Erkrankung.

A case of extranodal sinus histiocytosis with massive lymphadenopathy (ENSHML; Rosai-Dorfman disease) is reported. The patient presented with a history of intracranial tumour and exophthalmus. Clinical examination found a large mass in the left orbit and paranasal sinuses. Excisional biopsy showed a dense fibrous tissue with an infiltrate rich in macrophages. Further evaluation revealed a retroperitoneal mass with consecutive ureteral stenosis. Further histological and immunohistochemical investigation of the orbital mass, now in suspicion of a systemic disease showed an infiltrate of S-100-positive histiocytes and emperipolesis allowing the diagnosis of extranodal sinus histiocytosis. The correct histologic diagnosis was delayed due to the unusual and isolated extranodal localisation of the disease. The literature concerning extranodal manifestations of Rosai-Dorfman disease is reviewed. We suggest the additional evaluation of such rare and unusual cases in experienced reference centers.

Heat-shock protein 70 as a prognostic marker in node-negative breast cancer.

BACKGROUND: Heat-shock proteins (hsp) are involved in processes which are associated with tumour neogenesis and the biological behaviour of tumours. The object of our study was to investigate the significance of the 70 kDa hsp for the outcome of women with node-negative breast cancer. PATIENTS AND METHODS: Paraffin sections of 191 patients with operated breast cancer and a median follow-up of 177 months were stained immunohistochemically with a commercially available antibody against hsp70. RESULTS: We found a statistically significant correlation of the nuclear staining pattern with tumour size (> or < or = 2 cm; p = 0.046) and with a low tumour grading (G1 and G2 versus G3; p = 0.029). Patients showing a cytoplasmatic staining for hsp70 had a statistically significantly decreased overall survival [OS] (p = 0.04) and a shorter survival after recurrence [SR] (p = 0.026). CONCLUSION: The nuclear share of hsp70 is associated with various biological characteristics of malignant breast tumours, while the occurrence of cytoplasmatic hsp70 influences OS and SR.

Concomitant renal cell carcinoma with pituitary adenoma.

Renal cell carcinoma has a complex and variable natural history. We report a case underlining this who presented concomitant renal cell carcinoma metastasis with pituitary and adrenocortical adenomas. A 62-year-old woman presented with visual loss. Imaging revealed a large sellar mass with suprasellar extension. Four years before, nephrectomy and adrenalectomy had been performed for a renal cell carcinoma with metastasis in a coexistent adrenocortical adenoma. Faced with progressive visual loss and the questionable pituitary pathology, the patient underwent trans-sphenoidal surgery. Due to profuse tumor bleeding, only a biopsy was possible. In a second operation, the patient underwent craniotomy with subtotal resection of the tumor. Histological examination of the specimen revealed a metastasis of the renal cell carcinoma and a pituitary adenoma. The case presented here and a review of the reports suggest that there are some differences between the clinical features and outcomes of metastases of renal cell carcinoma and those of pituitary gland metastases from other primary sites.

Presentation of an unusual benign liver tumor: primary hepatic glomangioma.

Glomus organs are small arteriovenous anastomoses chiefly responsible for thermoregulation of the distal portion of the extremities. Glomangiomas are benign tumors of these bodies. They occur preferentially in the fingers and toes, but some case reports describe primary glomangiomas in the respiratory or gastrointestinal tract and genitals. To date, no glomangiomas of the liver have been reported. We report on a 61-year-old patient in whom routine ultrasound disclosed a subcapsular well-defined mass in the liver. Further imaging showed that the mass did not correspond to any of the usual liver tumors. Biopsy finally revealed it to be a primary glomangioma of the liver. Clinically, there was lack of appetite and weight loss over a period of several months. Owing to the possibility of malignant transformation of glomangiomas, as described in the literature, the tumor was excised under existing clinical symptoms and continued slow growth. Further histological evaluation of the tumor did not reveal malignancy. Primary glomangioma of the liver is a new differential diagnosis for benign liver neoplasms. Because there is a potential for malignant transformation, the existence of clinical symptoms and continuing growth are indications for resection.

Primary glomangioma of the liver: imaging findings.

Glomus organs are small arteriovenous anastomoses that are chiefly responsible for thermoregulation of the distal portion of the extremities. Glomangiomas are benign tumors of these bodies. Glomangiomas occur preferentially in the fingers and toes, but some case reports have described primary glomangiomas in the respiratory or gastrointestinal tract and the genitals. To date, no glomangiomas of the liver have been observed. We report on a 61-year-old patient in whom routine ultrasound disclosed a subcapsular well-defined mass in the liver. On imaging studies, no correspondence to the usual liver tumors was found. Magnetic resonance-guided biopsy showed a primary glomangioma of the liver. Clinically, the patient had no appetite and lost weight over several months. Due to the patient's weight loss and potential malignant transformation, the tumor was excised. Histologic work-up confirmed the diagnosis of a glomangioma with no signs of malignancy.

[Primary glomangioma of the liver. A new differential benign liver tumor diagnosis]. / Primäres Glomangiom der Leber. Eine neue Differenzialdiagnose benigner Lebertumoren.

Glomus organs are arteriovenous anastomoses which control the thermoregulation of the extremities. Benign tumors of these glomus organs, termed "glomangiomas", are therefore most frequently located in the fingers and toes. Case reports of primary glomangiomas in the respiratory- and gastrointestinal tracts as well as in the genital organs have been published. On the other hand, glomus tumors of the liver have not yet been described. We report the case of a 61-year-old patient with a smooth subcapsular lesion within the liver detected by a routine ultrasound scan. Further diagnostic imaging did not match with one of the common liver tumors. The diagnosis of a glomangioma was finally made by liver biopsy and subsequent histology. A review of the literature revealed a potential transformation of glomangiomas. Since the patient reported on inappetence weight loss and the tumor showed growth tendency, the indication for surgical excision was made. Final histologic investigation revealed no signs of malignancy. The primary glomangioma of the liver is a new differential diagnosis of benign liver tumors. As there is a possibility of malignant degeneration, we propose the decision for surgical removal once there are clinical symptoms and a growth tendency of the lesion.

[Ovarian epidermoid cyst and endometrioid carcinoma: do they share their origin?]. / Epidermoidzyste und endometrioides Karzinom des Ovars: Wo liegt ihr Ursprung?

A case of a well differentiated endometrioid adenocarcinoma of the ovary in combination with an epidermoid cyst is described. A typical epidermoid cyst without skin appendages could be observed. In direct neighborhood, there was a typical endometrioid carcinoma with some foci of squamous metaplasia. There was no continuum between the squamous metaplasia of the carcinoma and the wall of the epidermoid cyst. In addition, the benign cyst and the carcinoma shared some of their immunohistochemical profile. This case highlights the still unsolved question about the origin of epidermoid cysts and adds to the hypothesis that they arise from pluripotent coelomic epithelium.

Influence of donor MHC class I antigen expression on graft survival after rat parathyroid allotransplantation.

BACKGROUND AND AIMS: We investigated the influence of donor MHC antigen expression on graft survival after parathyroid transplantation in three different strain combinations. METHODS: MHC class I and II expression on parathyroid tissue of Lewis (LEW), Dark Agouti (DA), and Wistar-Furth (WF) rats was first analysed semiquantitatively by immunohistochemistry. Additionally, five groups were transplanted: (1) LEW to LEW, (2) DA to DA, (3) LEW to DA, (4) WF to LEW, and (5) DA to LEW. METHODS: MHC class I expression was strong in DA, moderate in WF, and weak in LEW rats; MHC class II expression was negative in all three strains. In the interstitium of all investigated tissue specimens, the proportion of MHC class II-expressing cells was low. RESULTS: After syngeneic transplantation, graft survival could be documented over the whole observation period. A mean graft survival of 20 (+/-2) days was observed following transplantation from LEW to DA, grafts in the group WF to LEW were rejected after 13 (+/-1) days, and graft function lasted 8 (+/-2) days in the group DA to LEW. The number of intragraft leukocytes expressing MHC class II molecules was equal in all groups, whereas increased levels of MHC class I on rat parathyroid tissue before transplantation resulted in a more rapid rejection. CONCLUSION: These results demonstrate that immunogenicity of rat parathyroid tissue seems to be determined by the amount of MHC class I expressed on donor parenchymal cells.

Rat parathyroid allotransplantation: Influence of MHC antigen expression on graft survival.

MHC antigen expression in parathyroid tissue and its influence on graft survival after allogeneic transplantation were investigated using a heterotopic rat transplantation model. MHC class I and II expression in parathyroid tissue of Lewis (LEW), Dark Agouti (DA), and Wistar-Furth (WF) rats was analysed semi-quantitatively by using immunohistochemistry. MHC class I expression was strong in DA, moderate in WF, and weak in LEW rats parenchyma, whereas MHC class II expression was negative. In the interstitium of all investigated tissue specimens, the proportion of MHC class II-expressing cells was low. Additionally, four groups were transplanted: 1) LEW to LEW, 2) DA to DA, 3) LEW to DA, and 4) WF to LEW. After syngeneic transplantation, graft survival could be documented over the whole observation period. A median graft survival of 20 (+/-2) days was observed after transplantation from LEW to DA, whereas grafts in the group WF to LEW were rejected after 13 (+/-1) days. The number of intra-graft leucocytes expressing MHC class II molecules was the same in all groups, whereas increased levels of MHC class I in parathyroid tissue before transplantation resulted in a more rapid rejection. These results indicate that immunogenicity of rat parathyroid tissue might be determined by the amount of MHC class I expressed in donor parenchymal cells. Further experiments are necessary to validate this observation.

Persistence of stable intragraft cell chimerism in rat liver allografts after drug-induced tolerance.

BACKGROUND: Drug-induced tolerance of rat liver allografts is well documented. We analyzed cellular events during immunosuppressive therapy on day (d) 10 and in the late phase (d 100) after transplantation to assess for characteristics in the intrahepatic leukocyte (IHL) population in the phase of tolerance. METHODS: Lewis rats served as recipients of Dark Agouti rat livers. Temporary immunosuppression with either cyclosporine (CsA) monotherapy (3 mg/kg/d) or triple therapy that consisted of a subtherapeutic CsA dosage (0.25 mg/kg/d) and monoclonal antibodies directed against the interleukin-2 receptor (IL-2R, CD25) and the intercellular adhesion molecule-1 (ICAM-1, CD54) was administered from postoperative d 0 to d 13. Cell migration and cell activation within liver grafts was assessed by standard histology and flow cytometry. IHL apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL). RESULTS: Both CsA monotherapy and triple therapy prolonged liver allograft survival to more than 100 d and led to the induction of donor-specific tolerance. Untreated recipients rejected their allografts within 14 d. In both groups, donor-specific IHLs initially dropped to 18% to 25% on d 10, but they rebounded to as much as 40% on d 100 as a common characteristic of both groups. Within this population, donor-specific T cells were dominant. In both groups, increased numbers of activated (IL-2R+) CD8+ T lymphocytes were present on d 100. No accumulation of apoptotic IHL was observed on d 100. Their proportion was unchanged in the triple therapy group and slightly decreased in the CsA group compared to the syngeneic controls. CONCLUSIONS: The present study reveals that tolerant liver allografts are repopulated by donor-specific T lymphocytes. This phenomenon is independent of the type of applied immunosuppression. The persistence of activated CD8+ T cells in the phase of proven donor-specific tolerance on d 100 indicates that liver tolerance is associated with the state of a permanent intragraft immune activation. It seems that the coexistence of donor cells with infiltrating recipient cells within liver grafts, termed intrahepatic cell chimerism, is characteristic for tolerated liver allografts.

A new rapid immunohistochemical staining technique using the EnVision antibody complex.

Rapid immunohistochemical investigation, in addition to staining with hematoxylin and eosin, would be useful during intraoperative frozen section diagnosis in some cases. This study was undertaken to investigate whether the recently described EnVision system, a highly sensitive two-step immunohistochemical technique, could be modified for rapid immunostaining of frozen sections. Forty-five primary antibodies were tested on frozen sections from various different tissues. After fixation in acetone for 1 min and air-drying, the sections were incubated for 3 min each with the primary antibody, the EnVision complex (a large number of secondary antibodies and horseradish peroxidase coupled to a dextran backbone), and the chromogen (3,3'diaminobenzidine or 3-amino-9-ethylcarbazole). All reactions were carried out at 37C. Specific staining was seen with 38 antibodies (including HMB-45 and antibodies against keratin, vimentin, leukocyte common antigen, smooth muscle actin, synaptophysin, CD34, CD3, CD20, and prostate-specific antigen). A modification of the EnVision method allows the detection of a broad spectrum of antigens in frozen sections in less than 13 min. This method could be a useful new tool in frozen section diagnosis and research. (J Histochem Cytochem 49:623-630, 2001)

Sclerosing cholangitis and liver cirrhosis after extrabiliary infections: report on three cases.

OBJECTIVE: To describe three unusual cases of sclerosing cholangitis after severe extrahepatic/extrabiliary bacterial infections. DESIGN: Case report, clinical. SETTING: Tertiary care intensive care unit (ICU). PATIENTS: Three patients admitted to the ICU with infections from Gram-positive bacteria followed by sclerosing cholangitis and secondary biliary cirrhosis. MAIN RESULTS: Three unusual cases of persisting cholestasis that occurred after bacterial infections originating from extrahepatic/extrabiliary foci are described. Endoscopic retrograde cholangiopancreatography and magnetic resonance cholangiopancreatography revealed multiple strictures of the intrahepatic bile ducts as a sign of sclerosing cholangitis. All patients progressed to biliary cirrhosis within months after the onset of cholestasis. CONCLUSION: Infection-associated cholestasis is usually a functional disorder and subsides after effective treatment of the underlying inflammatory focus. In rare cases, however, extrahepatic/extrabiliary infections may lead to sclerosing cholangitis and secondary biliary cirrhosis via unknown mechanisms.

Galactography and exfoliative cytology in women with abnormal nipple discharge.

OBJECTIVE: To evaluate galactography and cytology in women with nipple discharge without clinical or mammographic evidence of cancer. METHODS: During a 12.5-year period, 384 women (15-85 years, mean age 47.5 +/- 14 years) were referred for galactography and smear cytology for recent onset of spontaneous, non-milky nipple discharge. Patients with clinical or mammographic evidence of tumor underwent excisional biopsy directly. Among 314 galactograms, 189 [60.2%; 95% confidence interval (CI) 54.5%, 65.6%] biopsies were recommended. A further 11 patients were scheduled for biopsy because of mammography or cytology. RESULTS: Sixteen of 182 biopsied patients had malignancies (8.8%; CI 5.3%, 14.1%). Combined rate of papillomas, papillomatous proliferation, and malignant tumors was 59.9% (109 of 182; CI 52.4%, 67.0%). Biopsy was malignant in three of 56 women (5%) with nonhemorrhagic discharge and in 13 of 97 (13%) with hemorrhagic discharge (P =.26). Exfoliative cytology revealed 11 false-negatives, four false-positives, five true-positives, and 153 true-negatives (sensitivity 31.2%, CI 11%, 58%; specificity 97.4%, CI 93%, 99%). In ten of 158 patients (6.3%) with suspicious galactography, cancer was found by biopsy. Sensitivity of galactography for malignancy was 83% (CI 51.6%, 97.9%) and specificity was 41% (CI 35.2%, 46.5%). Galactographic sensitivity for any (benign or malignant) neoplasm was 94% (93 of 99; CI 87%, 98%) and specificity was 55% (119 of 215; CI 48%, 62%). Half of the cancers were detected exclusively by galactography. CONCLUSION: Cytology is helpful when positive and galactography localizes the source of discharge. Biopsy is indicated when palpation, mammography, cytology, or galactography is suspicious.

Predictive value of galactographic patterns for benign and malignant neoplasms of the breast in patients with nipple discharge.

The purpose was to identify features of malignant and non-malignant neoplastic breast disease on galactography and to estimate their predictive value. This is the largest reported study correlating galactographic morphological patterns with histopathology and the only blinded study. The study included 351 consecutive galactograms and 161 breast biopsies performed in patients with nipple discharge over a 10-year period. Three radiologists, blinded to clinical data and histological results, re-evaluated 158 previously performed galactograms of patients who had undergone excision biopsy. Extravasation or incomplete filling precluded reading in 9.5% of examinations. Among the remaining 143 examinations there were 11 cancers (7.7%), 56 papillomas (39.2%), 19 cases of intraductal papillomatous proliferation (13.3%), 55 cases of fibrocystic or secretory disease (38.5%) and two normals. A "filling defect/cut-off" pattern (n = 90) was found in 6 cancers (6.7%) and 58 cases of papilloma or papillomatous proliferation (64.4%). A "leafless tree" pattern was found only in benign cases (n = 12; 8.4%). In 32 of 143 cases (22.4%) a "ductal ectasia" pattern was present, in one case of which (3.1%) cancer was found. Cancer was identified in two of four cases with an "architectural distortion" pattern. Cancer is rare in patients with nipple discharge. A tendency towards a lower incidence of cancer associated with the "ductal ectasia" and "leafless tree" patterns was found. No statistical evidence was found to indicate that galactography provides an effective prospective diagnosis of malignancy. However, an abnormal galactogram strongly correlated (p < 0.001) with the presence of a breast neoplasm when both benign and malignant tumours were considered. The most important role played by galactography is in the localization of breast neoplasms and in the choice of appropriate surgical therapy.

Is the appearance of microcalcifications on mammography useful in predicting histological grade of malignancy in ductal cancer in situ?

It has been proposed that the grade of malignancy of ductal carcinoma in situ (DCIS) of the breast can be estimated by the morphology of microcalcifications found on mammography. We correlated microcalcifications and histopathology in a retrospective blinded review. We reviewed all patients who underwent excisional breast biopsy over a 5 1/2-year period. Mammograms and pathology slides of all patients (n = 49) with DCIS of the breast were included in a blinded retrospective analysis. Mammographic microcalcifications were divided into four categories, "linear branching", "coarse granular", "fine granular" or "no microcalcification". Independently, pathology specimens were assigned to poorly, intermediately and well differentiated categories according to the consensus classification of DCIS introduced by the European Organisation for the Research and Treatment of Cancer. Two patients had no microcalcifications. 25 (53%) of the remaining 47 patients had "linear branching" microcalcifications, 10 (21%) had "coarse granular" and 12 (25.5%) had "fine granular" microcalcifications. 19 patients (40%) had poorly differentiated, 23 (49%) intermediately differentiated and 5 (11%) well differentiated subtypes of DCIS. 14 (56%) of the 25 patients with "linear branching" microcalcifications had poorly differentiated DCIS, 10 (40%) had intermediately differentiated and 1 (4%) had well differentiated DCIS. 3 (30%) of 10 patients with "coarse granular" microcalcifications had poorly differentiated DCIS, 5 (50%) had intermediately differentiated and 2 (20%) had well differentiated DCIS. 2 (17%) of 12 patients with "fine granular" microcalcifications had poorly differentiated DCIS, 8 (67%) had intermediately differentiated and 2 (17%) had well differentiated DCIS. These findings were not statistically significant. In conclusion, "linear branching" microcalcifications tended to be associated with higher pathological grading. However, correlation was poor and there was considerable overlap between categories. Histological type of DCIS cannot be predicted prospectively on mammographic appearances.

Tolerance of rat liver allografts induced by short-term selective immunosuppression combining monoclonal antibodies directed against CD25 and CD54 with subtherapeutic cyclosporine.

BACKGROUND: Our purpose was to develop and evaluate protocols for selective immunosuppression after liver transplantation using the monoclonal antibodies (mAbs) NDS-61, directed against the interleukin-2 receptor (CD25), and 1A29, directed against the intercellular adhesion molecule-1 (CD54), in combination with subtherapeutic cyclosporine (CsA). METHODS: Orthotopic rat liver transplantation (ORLT) was performed in a DA-to-LEW strain combination. Immunosuppression was administered from day 0 to +13. Functional parameters such as survival time, body weight, and serum bilirubin levels were measured and the liver grafts were evaluated histologically. RESULTS: A stepwise tapering of CsA from 3 to 0.25 mg/kg/day reduced the long-term survival rate. All animals died at a CsA dosage of 0.25 mg/kg/day, which was therefore defined as subtherapeutic. Monotherapy with the anti-CD25 mAb was performed at dosages of 600 and 1800 microg/kg/day. The lower mAb dosage resulted in a long-term survival rate of 12% and was defined as subtherapeutic. The combination therapy of CsA (0.25 mg/kg/day) and anti-CD25 mAb (600 microg/kg/day) produced a synergistic effect and led to a long-term survival rate of 84%. This survival rate was significantly higher than those after either CsA (P<0.005) or anti-CD25 mAb (P<0.001) monotherapy. Both dosages (10 and 30 microg/kg/day) of anti-CD54 mAb monotherapy as well as anti-CD54 mAb combined with a subtherapeutic dosage of CsA were ineffective in preventing acute allograft rejection. The addition of anti-CD54 mAb (30 microg/kg/day) to combined CsA plus anti-CD25 mAb therapy (triple therapy), however, increased the long-term survival rate to 100%. In the triple therapy group there was no rejection process in the liver allografts at any time, and donor-specific tolerance could be shown by donor-specific and third-party heterotopic heart transplantation. CONCLUSIONS: The synergistic action of subtherapeutic CsA plus anti-CD25 mAb NDS-60 could be demonstrated, whereas anti-CD54 mAb only had a positive effect in a triple therapy group. Triple therapy prevented both acute and chronic rejection and induced donor-specific tolerance.