Primary malignant lymphoma of the breast: clinicopathological study of nine cases

Primary lymphoma of the breast is rare, accounting for 1.7-2.2% of extranodal lymphomas and 0.38-0.7% of non-Hodgkin's lymphomas (NHL). The aim of this study was to evaluate the clinicopathological features and treatment outcomes of patients with primary breast lymphomas (PBL). We conducted a retrospective review of the NHL cases diagnosed at Korea Cancer Center Hospital between 1989 and 2002. Nine (0.9%) of the 1,050 cases fulfilled the criteria for PBL. All patients were women (median age, 45 years) and usually presented with breast masses that had recently become enlarged. Six cases involved the breast alone (stage IE), whereas 3 cases also involved the ipsilateral axillary lymph nodes (stage IIE). Histopathologic studies revealed a diffuse large B cell lymphoma in 7 cases, marginal zone B cell lymphoma in 1 case, and small lymphocytic lymphoma in 1 case. Immunohistochemical analysis revealed a B-cell phenotype in all cases. There was no uniform approach to the treatment of PBL. Modified radical mastectomy and chemotherapy was performed in 4 cases, modified radical mastectomy and chemoradiotherapy was performed in 1 case, chemoradiotherapy alone, modified radical mastectomy alone, chemotherapy alone, and radiotherapy alone were performed in 1 case each. All cases achieved complete remission, but median overall survival was 12 months, showing very poor prognosis irrespective of the type of treatment modality.     

Metachronous non-Hodgkin's lymphoma in a patient with localized prostate cancer

Introduction A higher frequency of second malignancies is observed in patients with prostate cancer. We report a case of indolent non-Hodgkin's lymphoma diagnosed 2 years after prostate carcinoma. Case report A 65-year-old man with diagnosis of localized prostate adenocarcinoma was presented with fatigue 2 years after prostatectomy operation. Abdominal ultrasonography showed hepatomegaly and paraaortocaval, parailiac, and perivascular multiple lymph nodes. The complete blood count revealed anemia and thrombocytopenia. Bone marrow biopsy demonstrated small lymphocytic lymphoma. Conclusion Lymphoma should be suspected in cases with newly appeared adenopathy and/or cytopenias during follow-up. In patients with clinically organ-confined prostate cancer, indolent lymphoma should be in the differential diagnosis of newly appeared lymphadenopathy.     

Survivin expression is associated with features of biologically aggressive prostate carcinoma

BACKGROUND: Survivin counteracts cell death and controls mitotic progression. The objectives of the current study were to compare the expression patterns of survivin in normal prostate, primary prostate carcinoma, and lymph node tissues involved with prostate carcinoma and to determine whether the expression of survivin is associated with prostate carcinoma characteristics and progression. METHODS: Immunohistochemical staining for survivin and for transforming growth factor beta1 (TGF-beta1) and its receptors (types I and II; TGF-betaR1 and TGF-betaR2, respectively) was carried out on archival specimens from 114 consecutive patients who underwent radical prostatectomy (median follow-up, 64.8 months). Punch biopsies of the index carcinoma and normal tissue from each specimen were sectioned onto a single slide and stained. The authors also evaluated the expression of survivin in normal and malignant lymph node tissue from eight patients. RESULTS: Survivin was expressed in 41 of 114 normal prostate specimens (36%) from prostates that contained carcinoma, in 81 of 114 primary prostate carcinoma specimens (71%), in 3 of 8 normal lymphoid specimens (38%), and in 7 of 8 prostate carcinoma lymphoid specimens (88%). Survivin expression was associated with higher final Gleason sum (P = 0.001), loss of TGF-betaR1 and TGF-betaR2 expression (P = 0.041 and P = 0.008, respectively), and an increased risk of biochemical progression on univariate analysis (P = 0.0441). Among patients who had disease progression, survivin was expressed more commonly in those who had tumors with features of aggressive behavior. CONCLUSIONS: The expression of survivin gradually increased from normal prostate tissue, to low-grade primary carcinoma, to high-grade primary carcinoma and was highest in lymph node metastases. Survivin expression was associated further with alteration of the TGF-beta pathway and with overall and aggressive biochemical progression after radical prostatectomy.     

Is central nervous system prophylaxis necessary in ocular adnexal lymphoma?

PURPOSE: To examine the frequency of metastasis to the eye and central nervous system (CNS) from ocular adnexal lymphomas and to evaluate whether CNS prophylaxis is appropriate for these tumors. PATIENTS AND METHODS: Seventy-one patients with biopsy-confirmed ocular adnexal lymphomas were evaluated between 1989 and 1995. The lymphomas were subclassified histopathologically according to the new Revised European-American Lymphoma (REAL) criteria. Molecular genetic analysis of tumor cell DNA was done by Southern blot. Patients had a complete ophthalmologic evaluation and metastatic work-up and were then routinely followed up by an ophthalmologist and a medical oncologist. RESULTS: The 34 men and 37 women studied had a median age of 67 years (23 to 92). Ocular adnexal lymphomas were situated in the orbit in 54 patients, in the conjunctiva in 14 patients, and in the eyelid in 3 patients. Bilateral involvement occurred in 11 patients. The most common histologic diagnoses were (54 patients, 76%) extra-nodal marginal zone lymphomas and small lymphocytic lymphomas in 10 patients (14%). Molecular genetic analysis performed in all patients confirmed a monoclonal B-cell population in 55 patients (77%), including a single rearrangement of the immunoglobulin heavy chain gene in 14 patients, and more than two rearrangements in 41 patients. No patients had isolated T-cell gene rearrangements. Localized ocular adnexal lymphoma was diagnosed in 43 patients (61%), 17 patients (24%) were found to have concurrent extraocular lymphoma on metastatic work-up and 11 patients (15%) had a previous diagnosis of systemic lymphoma before the onset of their ocular tumor. The median duration of follow-up was 20 months. Overall, 32 patients (45%) had tumors, which remained localized to the orbit adnexa. Eleven patients (15%) relapsed, but none had eye or central nervous system involvement nor required CNS-directed therapy. Although eight patients died, only two died as a direct result of systemic lymphoma. No patient received CNS prophylaxis with either intrathecal chemotherapy and/or radiation therapy. CONCLUSION: Ocular adnexal lymphomas are rare non-Hodgkin's B-cell lymphomas. Metastatic involvement of the eye or central nervous system is rare and CNS prophylaxis with radiotherapy or chemotherapy is unnecessary.     

CD5 expression in a lymphoma of the mucosa-associated lymphoid tissue (MALT)-type as a marker for early dissemination and aggressive clinical behaviour.

Mucosa associated lymphoid tissue (MALT) developing in response to chronic infection or autoimmune stimuli has been recognized as a possible site of origin for a distinct type of B-cell lymphoma. While preferentially occurring in the stomach, MALT-type lymphomas can be found in virtually all organs. MALT-type lymphomas normally follow an indolent course, with a tendency to remain localized at their site of origin for a prolonged period of time. Histologically, MALT-type lymphomas are heterogeneous covering a cytological spectrum ranging from centrocyte-like cells to smaller lymphoid cells or monocytoid B-cells. Usually a small number of transformed blasts are also present. Immunohistochemically, the malignant cells express markers of B-cell lineage, but are distinct from follicular lymphomas (which express CD10), mantle cell lymphomas (expressing cyclin D1 and CD5) and small lymphocytic lymphoma, which express CD5 and CD23. In contrast to the usual phenotype CD20+CD10-CD5-Cyclin D1-, scattered reports in the literature have documented expression of CD5 in marginal zone B-cell lymphomas of MALT-type. However, these cases are rare, and aberrant CD5-expression has been thought to be a marker for early dissemination and aggressive behavior in some patients, while other reports have also found CD5 expression in localized indolent MALT-type lymphomas. We report a patient with a CD5+ MALT-type lymphoma following an aggressive clinical course without histological progression who relapsed only 18 months after local radiotherapy at the initial localizations (conjunctiva of the right upper eye lid and hypopharynx), and showed a rapid generalization to the contralateral conjunctiva, mediastinal lymph nodes and the esophagogastric junction. Our case lends further support to the notion that CD5+ MALT-lymphomas arising in the head-and-neck area and/or the ocular adnexa might be characterised by an aggressive clinical course.     

Primary breast lymphoma

Primary breast lymphoma (PBL) is a rare form of localized extranodal lymphoma. Few reports are available in the literature concerning its treatment and outcome. Of the 34 cases of PBL seen at our institution over a 25-year period, 20 consecutive cases were treated with CHOP or CHOP-like chemotherapy regimen and had adequate biopsy specimens for histological review. All these 20 PBL were of B-cell origin including one case of Burkitt lymphoma, and 2 cases of low-grade histologic type. Sixteen of the 20 patients achieved a complete remission (CR) and 2 achieved a partial remission (PR) (>75% tumor regression). Two patients had progressive disease while on therapy. With a median follow-up period of 80 months, 6 patients relapsed. Median time to relapse from diagnosis was 23 months (range, 3-41 months). Two of the relapses involved the central nervous system (CNS): isolated CNS relapse in one case and associated with other relapse sites in 1 case. The two patients who achieved a PR after chemotherapy also had disease progression to the CNS, 4 and 8 months after the end of CHOP chemotherapy. All 4 patients died of their disease 3, 6, 10 and 13 months after CNS involvement. Of the 16 centroblastic diffuse large B-cell lymphoma (DLCL), 3 had CNS disease at relapse. Three (15%) of our study patients developed a controlateral breast relapse. Twelve of the initial 20 patients were alive, including 11 with a persistent CR, 6 patients died of their lymphoma and 2 of unrelated diseases. In conclusion, we observed a high incidence of CNS relapse in this group of localized extranodal lymphoma, strongly suggesting that CNS prophylaxis should be associated with systemic chemotherapy in localized PLB.     

Preoperative plasma endoglin levels predict biochemical progression after radical prostatectomy.

PURPOSE: Endoglin (CD105) is a transmembrane glycoprotein expressed by human vascular endothelial cells thought to play a pivotal role in endothelial cell proliferation. The aim of this study was to evaluate the association of preoperative plasma endoglin levels with established clinical and pathologic features of prostate cancer and disease progression after radical prostatectomy. EXPERIMENTAL DESIGN: Preoperative plasma endoglin levels were measured in 425 patients who underwent radical prostatectomy for clinically localized prostate cancer using a commercially available ELISA assay. Multivariate logistic regression was used to test the association of plasma endoglin levels with biochemical progression after radical prostatectomy. RESULTS: Median follow-up for patients alive at the time of analysis was 36.8 months (interquartile range, 44.1). Of 425 patients, 77 patients (18.1%) experienced biochemical progression after radical prostatectomy. Preoperative plasma endoglin levels were significantly elevated in patients with higher preoperative total serum prostate-specific antigen (P < 0.001) and adverse pathologic features. Preoperative plasma endoglin was an independent predictor of biochemical progression after surgery after adjusting for the effects of standard preoperative and postoperative features (P < 0.001 and P = 0.026, respectively). CONCLUSIONS: Preoperative plasma endoglin levels are associated with established features of advanced prostate cancer. More importantly, higher preoperative plasma endoglin levels are independent predictors of an increased risk of biochemical progression in patients treated with radical prostatectomy and bilateral pelvic lymphadenectomy.     

Nasopharyngeal lymphoid hyperplasia after therapy for childhood lymphomas

Although diffuse thymic hyperplasia after therapy has been reported in lymphomas, no report is found in the medical literature about hyperplasia of other lymphoid tissues following chemotherapy in malignancies as far as we could reach. So, we planned to investigate the nasopharyngeal region of the lymphoma cases during their follow-up while at remission. Children who were in follow-up after cessation of oncological therapy with the diagnosis of lymphoma were evaluated for their nasopharyngeal lymphoid tissues by means of computed tomography. When a mass lesion was diagnosed, biopsies were taken. Among 23 lymphoma cases in follow-up, at a median of eight months (range 1-13 months), eight patients (six Hodgkin's and two Non-Hodgkin's malignant lymphoma) developed nasopharyngeal lymphoid hyperplasia (34.78%) that were proven to be benign by means of biopsies. Two of the patients also developed thymic hyperplasia. Nasopharyngeal hyperplasia regressed in four patients at a median of four months. Nasopharyngeal lymphoid hyperplasia may be diagnosed after the cessation of therapy in lymphomas and whatever the cause, it seems to be a benign process.     

Phase II study of proteasome inhibitor bortezomib in relapsed or refractory B-cell non-Hodgkin's lymphoma.

PURPOSE: Evaluate efficacy and toxicity of bortezomib in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma. PATIENTS AND METHODS: Patients were stratified, based on preclinical data, into arm A (mantle-cell lymphoma) or arm B (other B-cell lymphomas) without limitation in number of prior therapies. Bortezomib was administered as an intravenous push (1.5 mg/m2) on days 1, 4, 8, and 11 every 21 days for a maximum of six cycles. RESULTS: Sixty patients with a median number of prior therapies of 3.5 (range, one to 12 therapies) were enrolled; 33 patients were in arm A and 27 were in arm B, including 12 diffuse large B-cell lymphomas, five follicular lymphomas (FL), three transformed FLs, four small lymphocytic lymphomas (SLL), two Waldenstrom's macroglobulinemias (WM), and one marginal zone lymphoma. In arm A, 12 of 29 assessable patients responded (six complete responses [CR] and six partial responses [PR]) for an overall response rate (ORR) of 41% (95% CI, 24% to 61%), and a median time to progression not reached yet, with a median follow-up of 9.3 months (range, 1.7 to 24 months). In arm B, four of 21 assessable patients responded (one SLL patient had a CR, one FL patient had a CR unconfirmed, one diffuse large B-cell lymphoma patient had a PR, and one WM patient had a PR) for an ORR of 19% (95% CI, 5% to 42%). Grade 3 toxicity included thrombocytopenia (47%), gastrointestinal (20%), fatigue (13%), neutropenia (10%), and peripheral neuropathy (5%). Grade 4 toxicity occurred in nine patients (15%), and three deaths from progression of disease occurred within 30 days of withdrawal from study. CONCLUSION: Bortezomib showed promising activity in relapsed mantle-cell lymphoma and encouraging results in other B-cell lymphomas. Future studies will explore bortezomib in combination with other cytotoxic or biologic agents.     

Patterns of failure in primary testicular non-Hodgkin's lymphoma

Patterns of failure were analyzed in 30 patients with testicular non-Hodgkin's lymphoma: 16 had stage IE disease, ten had stage IIE, and four had stage IV. After orchiectomy, two of the 16 patients with stage IE disease received no additional therapy, one received multiagent chemotherapy, and 13 received pelvic and para-aortic radiation. Twelve patients with stage IE disease had progression, and the median time to progression was 12 months. Of the 14 patients with extratesticular involvement (stage IIE or IV), one (stage IV) received no treatment after orchiectomy, three (stage IIE) received para-aortic and pelvic radiation, and ten (seven stage IIE and three stage IV) received multiagent chemotherapy with or without radiation. Eight of the patients with stage IIE or IV disease had progression, and the median time to progression was 11 months. Widespread extranodal progression was observed in 17 of the 20 patients who had progression. The tendency of testicular lymphoma for early systemic progression suggests a need for multiagent chemotherapy in initial management.     

Surgical pathology examination of radical prostatectomy specimens. Updated protocol based on the Italian TAP study

Between January 1996 and June 2000, 192 men with prostate cancer underwent radical retropubic prostatectomy (RP) and bilateral pelvic node dissection in 26 centers participating in the Italian randomized prospective TAP study. The reviewing pathologist evaluated 145 RP specimens. Seventy-five cases had not been treated with total androgen ablation before RP was performed, whereas 70 had been treated for three months. Whole-mount sectioning of the complete radical prostatectomy specimens was adopted in each center for accurately evaluating the pathological stage of prostate cancer and resection limit status. The results of this study suggest that total androgen ablation before RP is beneficial in men with clinical stage T2 because of the significant pathological down-staging and decrease in the number of positive margins in the RP specimens. On the basis of the experience acquired through the Italian TAP study and recent publications on prognostic factors in prostate cancer, the original practice protocol for examination of RP specimens removed from patients with carcinoma of the prostate glands was updated.     

Vascular endothelial growth factor receptor 1 expression in pelvic lymph nodes predicts the risk of cancer progression after radical prostatectomy

Recent studies suggest that vascular endothelial growth factor receptor (VEGFR) 1-positive hematopoietic progenitor cells precede the arrival of tumor cells and form clusters that may portend sites of future metastatic disease. The aim of the present study was to clarify whether VEGFR1 expression in pelvic lymph nodes predicts the risk of prostate cancer progression after radical prostatectomy. VEGFR1 expression in pelvic lymph nodes was examined by immunohistochemistry in 95 patients who underwent radical prostatectomy for prostate cancer. A cluster of VEGFR1-positive cells was considered positive. Expression of VEGFR1 in pelvic lymph nodes and biochemical recurrence after radical prostatectomy were examined by univariate survival analysis and multivariate Cox proportional hazards regression analysis. Thirty-seven of 79 lymph node-negative patients (46.8%) were found to have VEGFR1-positive cells in their pelvic lymph nodes, whereas 16 of 16 lymph node metastasis-positive patients (100%) had VEGFR1 clusters. There was a significant correlation between pathological stage and VEGFR1 staining ( P =  0.002). Univariate analysis showed that pathological stage ≥pT3 and VEGFR1 expression in pelvic lymph nodes were each significantly associated with biochemical recurrence after radical prostatectomy. Multivariate analysis showed VEGFR1 expression to be an independent predictor of biochemical recurrence after radical prostatectomy (risk ratio = 5.715, P  = 0.010), as was preoperative prostate-specific antigen (PSA) level ≥10 ng/mL. Although larger validation studies are required, our results suggest that VEGFR1 expression in pelvic lymph nodes predicts the risk of biochemical PSA recurrence after radical prostatectomy. ( Cancer Sci 2009; 100: 1047–1050)     

The utility of interphase fluorescence in situ hybridization for the detection of the translocation t(11;14)(q13;q32) in the diagnosis of mantle cell lymphoma on fine-needle aspiration specimens

BACKGROUND: Mantle cell lymphoma can be difficult to differentiate cytologically from other small cell non-Hodgkin lymphomas. Nevertheless, the distinction is important, because mantle cell lymphoma is more aggressive than other small cell non-Hodgkin lymphomas. The purpose of this study was to determine whether fluorescence in situ hybridization (FISH) is helpful in diagnosing mantle cell lymphoma on fine-needle aspiration (FNA) specimens by detecting the t(11;14)(q13;q32) translocation that is characteristic of this tumor. METHODS: Fifty-five lymph node FNA specimens from 53 patients were analyzed using FISH. A 2-color FISH assay that employed probes at the 14q32 (immunoglobulin H) and 11q13 (dual-colored, directly labeled cyclin D1) loci was used. The number of single-fusion and double-fusion signals in 200 cells was counted. If > or = 14% single-fusion signals or > or = 1.5% double-fusion signals or both were present, then the sample was considered FISH positive. The findings were correlated with the cytologic, histologic, and immunophenotypic findings in each specimen. RESULTS: Of the 55 cytology specimens, 17 were mantle cell lymphomas, and 38 were nonmantle cell lymphomas, including 16 small lymphocytic lymphomas (9 of 16 in an accelerated phase), 5 large cell lymphomas, 5 follicular lymphomas, 7 transformed large cell lymphomas (Richter syndrome), 3 atypical lymphoid proliferations, and 2 low-grade B-cell lymphomas. All 17 mantle cell lymphomas were positive by FISH. In addition, there were six small lymphocytic lymphomas (two in accelerated phase), one transformed large cell lymphoma, and one large cell lymphoma of follicular origin positive by FISH. The mean number of single-fusion and double-fusion signals, respectively, was 36 and 33 in mantle cell lymphoma specimens and 19 and 3 in positive nonmantle cell lymphoma specimens. CONCLUSIONS: The detection of the t(11;14)(q13;q32) translocation by FISH analysis was helpful in diagnosing mantle cell lymphoma on FNA specimens. Double-fusion signals were more specific for mantle cell lymphoma than single-fusion signals. In rare instances, other non-Hodgkin lymphomas also showed increased numbers of single-fusion signals that were not necessarily indicative of the t(11;14)(q13;q32) translocation. Therefore, in an initial diagnosis of mantle cell lymphoma, significant numbers of double-fusion FISH signals should be identified and interpreted in conjunction with the cytologic and immunologic studies.     

Primary malignant lymphomas of the breast.

Fourteen cases of primary malignant lymphomas of the breast were found in the pathology files of the M. D. Anderson Hospital and Tumor Institute from 1944 to 1975. The lymphomas represented only 0.12% of 11,277 primary malignant breast tumors seen during the same period. There were no definite clinical features to distinguish the patients with lymphoma from those with breast carcinoma. All of the lymphomas had a diffuse pattern. Eight cases were classified as undifferentiated lymphoma, five as histiocytic, and one as poorly differentiated lymphocytic, convoluted cell type. Four patients had mastectomies and the remainder biopsies as their sole surgical procedure. Eight patients received post-surgical radiotherapy and all eventually had chemotherapy. The five-year survival rate for the 13 patients with follow-up was 49%. Patients with histiocytic lymphoma appeared to have a more favorable prognosis than those with the undifferentiated type. Six of the latter patients are dead with a median survival of seven months, comparable to the reported survival of patients with American Burkitt's lymphoma. The patient with the convoluted cell type has developed acute blastic leukemia and is currently under therapy.     

Effective palliation by low dose local radiotherapy for recurrent and/or chemotherapy refractory non-follicular lymphoma patients

In this work, we have studied the response rates and duration of response after low-dose (4 Gy) involved field radiotherapy (LD-IF-RT) in relapsed or chemotherapy refractory indolent and aggressive lymphoma patients. 71 patients (177 symptomatic sites) received LD-IF-RT consisting of 39 males and 32 females with a median age of 69 years (range 43-93). Patients included were those with small lymphocytic lymphoma/chronic lymphocytic leukaemia (n=23), marginal zone lymphoma, nodal type (n=18), mantle cell lymphoma (n=17), and diffuse large B-cell lymphoma (n=13). Bulky disease (5 cm) was present in 73% of all patients. A median of two prior chemotherapy regimens (range 0-10) preceded LD-IF-RT. Median time since diagnosis was 31 months (range 1-216 months). Time to (local) progression was calculated according to the Kaplan-Meier method. Differences in response rates were compared using the chi2-test. The results showed that overall response rate was 87%; complete remission (CR) was reached in 34 patients (48%) and a partial remission (PR) in 28 patients (39%). Stable disease (SD) was maintained in nine patients (13%). The median time to progression (TP) was 12 months and the median time to local progression (TLP) was 22 months. The 34 CR patients showed a median TP of 16 months and a median TLP of 23 months. None of the factors studied (age, sex, lymphoma subtype, radiotherapy regimen, number of prior regimens or time since diagnosis, number of positive sites or largest lymphoma diameter) were found to relate to response. At time of death 70% of patients were without in-field progression after LD-IF-RT. It appears that LD-IF-RT is a valuable asset in the management of relapsed disease in both indolent and aggressive lymphoma and should be considered to palliate symptoms in patients with recurrent and/or chemotherapy refractory disease.     

Primary malignant lymphoma of the uterus: a case report and review of the literature

Primary malignant lymphomas in the female genital tract are rare. Most cases are non-Hodgkin lymphomas of which diffuse large B-cell lymphomas are most commonly seen. Symptoms are associated with other, more common diseases; therefore, a doctors' delay can be expected. In this case a woman presented with complaints of urinary obstruction due to a large tumour in the pelvic area. A laparotomy was performed. A very large tumour of the uterus was found with adherence to the pelvic wall and urinary bladder. Diagnostic histological examination showed a diffuse large B-cell lymphoma. Treatment with R-CHOP chemotherapy was started shortly after the operation. The treatment of patients with a primary malignant lymphoma of the uterus should be individualized with the following options: surgery, radiotherapy and/or chemotherapy.     

Synchronous bilateral breast cancer in a male patient following hormone therapy for prostate cancer

We report an unusual case of bilateral, synchronous breast cancer in a male patient who had a history of estrogen therapy for prostate cancer. A 64-year-old Japanese man was diagnosed with T1N0M0 prostate cancer and received a total prostatectomy. Twenty months after the resection, the patient developed multiple bone metastases, and received radiation therapy, systemic chemotherapy, and hormone therapy for 15 months. After completing this treatment, he was diagnosed with T1N0M0 primary breast cancer in his left breast and underwent a modified mastectomy. Five months after the mastectomy he received systemic chemotherapy followed by estrogen therapy because of the progression of prostate cancer. Three months after this treatment, he was diagnosed with T1N0M0 primary breast cancer in his right breast. To the best of our knowledge, this is a rare case of synchronous bilateral male breast cancer following hormone therapy for prostate cancer.     

Expression of the p53 and Maspin protein in primary prostate cancer: correlation with clinical features

The serine protease inhibitor Maspin has been reported to inhibit the invasiveness and motility of prostate cancer tumor cells. Additionally, a p53-dependent regulatory pathway of Maspin in prostate cancer cell lines has been indicated. The first aim of our study was to determine the prognostic value of Maspin protein expression for the recurrence-free survival of patients undergoing radical prostatectomy for the treatment of clinically localized prostate cancer. Secondly, Maspin expression was correlated to p53 protein expression in order to gain additional information on a possible and previously suggested regulatory influence of the wild-type p53 protein on the Maspin protein expression. Tumor specimens obtained from 84 patients undergoing radical prostatectomy for localized prostate cancer were investigated for the expression of the Maspin and p53 protein by an immunohistochemic approach. Maspin protein expression was correlated with further patients' and tumor characteristics such as tumor stage, histologic grading, regional lymph node status, p53 protein expression and recurrence-free survival of the patients following radical prostatectomy. After a median follow-up of 64 months (24-197 months), 23 of 40 patients (58%) with a negative or decreased Maspin expression (group 1) developed local recurrence or systemic tumor progression in contrast to 8 of 44 patients (18%) with a retained expression of the Maspin protein (group 2) (p = 0.02; log-rank test). The median recurrence-free survival following radical prostatectomy was 26 months (12-37 months) for group 1 patients and 41 months (5-134 months) for patients from group 2 (p = 0.04). A positive immunohistochemic staining reaction for the p53 protein was significantly correlated with a decreased expression of the Maspin protein (p = 0.015; Spearman correlation coefficient). Additionally, loss of Maspin protein expression was correlated to higher tumor stages (p = 0.002) and an increasing histologic dedifferentiation (p = 0.03). This is the first study to indicate that Maspin protein possibly functions as a clinically relevant inhibitor of tumor progression, preventing the local invasiveness and further systemic progression of prostate cancer. Our investigation delivers first hints for a p53-dependent regulatory pathway of the Maspin protein in human prostate cancer.     

Dedifferentiation in the metastatic progression of prostate carcinoma.

BACKGROUND: Dedifferentiation is a distinctive feature of cancer progression. Detailed histologic analysis of primary prostate carcinoma and synchronous lymph node metastases may improve our understanding of the complex process of cancer progression and metastasis. METHODS: The authors studied 242 regional lymph node positive prostate carcinoma patients who underwent radical prostatectomy and bilateral lymphadenectomy between 1987 and 1992 at the Mayo Clinic. Patients ranged in age from 47-79 years (median, 66 years). The median follow-up was 6.1 years. Gleason scores of lymph node metastases and primary tumors were compared and correlated with systemic disease progression. Histologic dedifferentiation was defined as a higher Gleason grade in the lymph node metastases than in the primary tumor. Systemic disease progression was defined as the presence of distant metastases documented by biopsies, abdominal computed tomography, plain radiograph, or bone scan. RESULTS: The 5-year systemic progression free survival (PFS) rate was 90%. The Gleason score in the lymph node metastases was higher than in the primary tumor in 45% of patients, lower in 12% of patients, and matched exactly in 43% of patients. The 5-year PFS was significantly different between patients with histologic dedifferentiation (88% +/- 3) and those without dedifferentiation (94% +/- 2) (P = 0.04). Adjusting for the Gleason grade of the primary tumor and total lymph node tumor volume, the relative risk for disease progression associated with dedifferentiation was 1.8 (95% confidence interval, 0.7-4.7; P = 0.25). CONCLUSIONS: The findings of the current study demonstrate the morphologic heterogeneity of metastases from prostate carcinoma. There is a trend toward histologic dedifferentiation when prostate carcinoma metastasizes to regional lymph nodes. This dedifferentiation, although univariately significant, was not associated with disease progression when adjusted for lymph node tumor volume.