Diffuse follicle center lymphoma of the spine: a primary epidural lymphoma?

A 72-year-old right-handed woman presented with a 6-month history of right thoracic wall discomfort. An MRI of the thoracic spine showed a small dumbbell-shaped mass centered within the right T7-8 foramen. The patient was asked to return to clinic for reevaluation to include a new MRI of the thoracic spine in 6 months. She did not comply with this recommendation and 1 year later, she presented with increasing difficulty ambulating and spastic paraparesis. A follow-up MRI of the thoracic spine now demonstrated significant interval growth of the mass with an extra-foraminal component extending into the thoracic cavity. She was taken to the operating room for resection of the epidural tumor. The pathology was consistent with diffuse follicle center lymphoma as cells were immunohistologically positive for CD20, CD 10, BCL-2 and BCL-6. Primary spinal follicle center lymphomas of the spine are rare with the current case being the first diffuse follicle center type reported in the literature.

Botryoid-type of embryonal rhabdomyosarcoma of renal pelvis in an adult. A case report and review of the literature.

A case of botryoid-type embryonal rhabdomyosarcoma of the renal pelvis in a 49-year-old woman is reported. The tumor led to hydronephrosis. The surgical resection specimen disclosed a translucent, polypoid mass attached to the wall of the renal pelvis by thin stalk. Light-microscopic examination revealed a large exophytic polypoid tumor with intact surface epithelium, which was negative for dysplasia or carcinoma in situ. There was a condensation of epithelioid to spindle cells underneath the basement membrane, forming a cambium layer. The core of the lesion contained interspersed epithelioid to spindle cells with myxoid change and edema. Cells of the cambium layer as well as interspersed cells in the core exhibited marked cytologic atypia with mitotic figures. Immunohistochemical stains for cytokeratin, S-100 and myoglobin were negative, stains for desmin and actin were positive. Although botryoid-type embryonal rhabdomyosarcomas have been reported to occur at various sites in the genital tract and lower urinary tract, to our knowledge, this is the first reported case of the tumor within the renal pelvis. Also, the occurrence of these tumors in adults is quite rare.

Five years of complete remission of gastric diffuse large B cell lymphoma after eradication of Helicobacter pylori infection.

Long term follow up data are not available for cases of diffuse large B cell gastric lymphoma treated by eradicating Helicobacter pylori alone. We present the case of an 82 year old man with diffuse large B cell lymphoma localised to the stomach which responded to H pylori eradication and which has not recurred after more than five years of close follow up. Our patient was not a candidate for other modalities of treatment. This case demonstrates that the option of treating H pylori infection as the initial trial of treatment for localised diffuse large B cell lymphoma is appropriate for consideration. If medical therapy using eradication of H pylori is used, it is essential that the patient undergoes close observation and repeated surveillance endoscopies.

Staged resection of bilateral pleuropulmonary blastoma in a two-month old girl.

Pleuropulmonary blastoma is a rare unilateral intrathoracic tumor of childhood. We report an unusual case of bilateral pleuropulmonary blastoma in a two-month old girl who underwent staged thoracotomies for complete wedge resection of both neoplasm. She remains well and tumor free two years after the operation.

Oral combination chemotherapy in conjunction with filgrastim (G-CSF) in the treatment of AIDS-related non-Hodgkin's lymphoma: evaluation of the role of G-CSF; quality-of-life analysis and long-term follow-up.

In 1993 we reported the efficacy and toxicity profile of an oral combination regimen administered to 18 patients with AIDS-related lymphoma (NHL-1 study). We observed a 61% response rate; 39% one-year survival rate; nearly two-thirds of patients developed > or = grade 3 leukopenia; and 28% of cycles were associated with febrile neutropenia. These results prompted us to shorten the duration of therapy and to add G-CSF to ameliorate the myelosuppression. Twenty patients with biopsy-proven AIDS-related lymphoma were treated with three 6-week cycles of oral chemotherapy consisting of lomustine (CCNU) 100 mg/m2 on day 1, cycles no. 1 and 3; etoposide 200 mg/m2 days 1-3; cyclophosphamide and procarbazine both 100 mg/m2 days 22-31; and G-CSF 5 microg/kg subcutaneously days 5-21 and days 33-42 (NHL-2 study). The following analyses were undertaken: (1) evaluation of toxicity and efficacy parameters for patients in the current (NHL-2) study; (2) analysis of the clinical role of G-CSF by (historical) comparison with the NHL-1 study of the same regimen without G-CSF; (3) quality-of-life assessments using the Functional Living Index-Cancer (FLIC) and Brief Symptom Inventory (BSI) instruments for all 38 patients (NHL-1+2); and (4) long-term follow-up for all 38 patients. In the current study the overall objective response using ECOG criteria was 70% (95% CI, 50-90%) with 6 CRs (30%) and 8 PRs (40%). The median survival duration was 7.3 months (range: 0.5-51+ months). One patient developed CNS relapse. There were no significant differences with respect to demographics or prognostic factors between the patient populations of the NHL-1 study and the current study (P > 0.2 for each factor). Myelosuppression was the major toxicity in both studies. In the current study versus the NHL-1 study, although the lower incidences of grade 3/4 myelosuppression (51% vs. 64%) and febrile neutropenia (17% vs. 28%) on a per cycle basis were not statistically significant, fewer patients (40% vs. 60%) were affected. However, the severity of myelotoxicity was lessened with the addition of G-CSF, measured in terms of the discontinuation of therapy, myelotoxic deaths, and freedom from grade 3/4 myelotoxicity ( P < 0.02). The number of hospitalizations for febrile neutropenia (7 in the NHL-2 study vs. 13 in the NHL-1 study) was also significantly different (P < 0.05). Quality-of-life analysis confirmed no significant functional or psychological deterioration during therapy except for patients experiencing febrile neutropenia, whose functional capacity deteriorated (P < 0.04). The 1-year, 18-month, and 2-year survival rates for the combined studies (38 patients) were 32%, 21%, and 13%, respectively. At time of death 49% of patients were free from progression of their lymphoma. Administration of the oral regimen has resulted in 13% of patients surviving two years, and half of patients surviving free from progression of their lymphoma. This regimen is efficacious and considerate of patient quality-of-life issues. The addition of G-CSF to the regimen decreases the frequency of hospitalization for febrile neutropenia.

Needle biopsy DNA ploidy status predicts grade shifting in prostate cancer.

DNA ploidy analysis of prostate needle biopsy specimens was performed to determine whether ploidy status could predict tumor grade shifting at radical prostatectomy. The paired needle biopsy and radical prostatectomy specimens from 111 randomly selected men with prostate cancer were obtained from the surgical pathology files of the Albany Medical Center Hospital. The original tumor grades were assigned by a staff of 12 surgical pathologists according to the Gleason system. Tumors with original Gleason scores < or = 6 were classified as low grade, and tumors with scores of > or = 7 were considered high grade. DNA ploidy analysis was performed on the needle biopsy specimens using the CAS 200 image analyzer (Becton Dickinson Immunocytometry Systems, Mountain View, CA, USA) on Feulgen stained 5-microm tissue sections. There were 88 diploid and 23 nondiploid cases. Thirty-eight of 111 (34%) of cases had grade shifting from needle biopsy to radical prostatectomy specimens. Of 89 low-grade needle biopsy cases, 28 (31%) were upgraded at radical prostatectomy. Of 22 high-grade needle biopsy cases, 10 (45%) were downgraded to low grade at radical prostatectomy. Of the 28 low-grade needle biopsy specimens that were upgraded at radical prostatectomy, 19 (68%) featured an aneuploid histogram and 9 (32%) were diploid. Nineteen of 28 (68%) of aneuploid low-grade tumors on needle biopsy became high-grade at radical prostatectomy. Nine of 10 (90%) diploid high-grade tumors at needle biopsy became low-grade at radical prostatectomy. Of the 38 cases in which ploidy and grade were incongruous, 28 (74%) had grade shifting. In a multivariate regression analysis, a high-grade Gleason score on radical prostatectomy specimens correlated significantly with needle biopsy ploidy (p = 0.0001) but not with needle biopsy grade (p = 0.15). The sensitivity of the needle biopsy grade in the detection of high-grade tumors on radical prostatectomy was 30%, and the specificity was 86%. The sensitivity of ploidy status in the prediction of high grade at radical prostatectomy was 78%, and the specificity was 96%. With a prostate-specific antigen (PSA) level of >0.4 ng/ml as the indicator of post-radical prostatectomy disease recurrence on a subset of 106 patients, on univariate analysis, disease recurrence was predicted by needle biopsy ploidy (p = 0.001) and radical prostatectomy grade (p = 0.04) but not by needle biopsy grade (p = 0.39). On multivariate analysis, needle biopsy DNA ploidy status independently predicted disease recurrence (p = 0.002), whereas needle biopsy and prostatectomy grade did not. These results indicate that DNA ploidy analysis of needle biopsy specimens of prostate cancer predicts grade shifting, that it is a more sensitive and specific indicator of final tumor grade at radical prostatectomy than is the original needle biopsy grade, and that ploidy status independently predicts postoperative disease recurrence.

Oral combination chemotherapy in the management of AIDS-related lymphoproliferative malignancies.

An oral combination chemotherapy regimen initially developed for AIDS-related non-Hodgkin's lymphoma includes lomustine (CCNU), etoposide, cyclophosphamide, and procarbazine. This regimen takes advantage of oral administration, the in vitro synergy of these drugs and their first-line efficacy in lymphoma, and the ability of lomustine and procarbazine to cross the blood-brain barrier. This regimen was used to treat 38 patients with AIDS-related non-Hodgkin's lymphoma. The overall objective response rate was 66% (34% complete response rate) with a 5% CNS relapse rate, and a median survival duration of 7.0 months. One-third of the patients survived for 1 year, 11% for 2 years, and half of the patients survived free from progression of their lymphoma. On the basis of these results, this oral regimen was modified and administered to 5 patients with AIDS-related primary CNS lymphoma as part of a sequential combined-modality chemotherapy and radiation regimen. Rapid progression of CNS disease was observed in this group of patients, with a median survival duration of 1.0 month. The identical regimen was administered to 7 patients with AIDS-related Hodgkin's disease: we observed a 71% partial remission rate and a median survival duration of 7.0 months. Myelosuppression remains the most significant clinical toxicity. Our results with this oral regimen appear comparable to those of standard intravenous combination chemotherapy regimens in patients with AIDS-related non-Hodgkin's lymphoma.

Altered p53 is associated with aggressive behavior of chondrosarcoma: a long term follow-up study.

BACKGROUND: p53 is a major tumor suppressor gene that has been implicated in the biology of a variety of human neoplasms, including some that affect the skeleton. Recent studies based on small numbers of cases have shown that overexpression or alteration of the p53 gene is frequently present in high grade, clinically aggressive chondrosarcomas of bone. In this study, the authors addressed the relation between overexpression and alteration of the p53 gene and the clinical aggressiveness of chondrosarcoma in a large series of patients for whom long term follow-up data were available. METHODS: The authors analyzed the expression and/or alteration of the p53 gene in 158 cases of chondrosarcoma of bone using immunohistochemistry, single-strand conformation polymorphism, and direct sequencing. They then related the findings to various clinicopathologic parameters and long term follow-up data. RESULTS: The presence of overexpression and/or structural alterations of the p53 gene was documented in 38.1% of chondrosarcomas of bone. A statistically significant correlation was observed between overexpression or alteration of the p53 gene and both the histologic grade of the tumor and the presence of metastasis. The probability of local recurrence free, metastasis free, and overall survival was significantly higher for patients with no overexpression or alteration of p53 than for patients with p53 overexpression or alteration. CONCLUSIONS: Overexpression or alteration of the p53 gene is an important predictor of aggressive clinical behavior in chondrosarcoma of bone.

Histologically pure seminoma with elevated alpha-fetoprotein: a clinicopathologic study of ten cases.

Seminomas account for 50% of testicular germ-cell tumors, and more than 90% of these are classic seminomas. When patients with a histologically pure testicular seminoma show an elevated level of serum á-fetoprotein (AFP), it is generally assumed that an undetected focus of yolk sac tumor (YST) is present and the patient is managed with a treatment regimen for non-seminomatous tumor. We studied 10 cases of histologically pure seminoma with elevated levels of serum AFP in an attempt to identify any distinctive clinical, histopathologic, or immunohistochemical features. The patients ranged in age from 27 to 48 years (mean, 31 years). Eight patients had primary tumors of the testis, and two presented with supraclavicular and ileal tumors. The clinical stage at presentation varied: four tumors were stage I, four were stage II, and two were stage III. Serum levels of AFP were elevated in all patients at ranges of 10.4 to 16 ng/ml (mean, 12.0 ng/ml). In all patients, the primary tumors and metastases when present exhibited classic seminoma histology without other germ-cell components. The tumor cells expressed keratin in seven cases. The pattern of keratin immunoreactivity ranged from focal staining in five cases to moderate staining in two cases. All cases were negative for AFP, and the nine cases in which staining for CD30 (Ki-1) was performed were also negative. All four patients with stage I tumors underwent the conventional therapy for pure seminoma, i.e., orchiectomy and subsequent radiation therapy. Five patients received treatment for non-seminomatous tumors, i.e., chemotherapy after orchiectomy. Extensive work-up failed to detect the primary tumor in one patient, and he was treated for a non-seminomatous tumor, undergoing chemotherapy and irradiation. All patients are alive and well, and none has developed evidence of YST at a mean follow-up of 6 years (range, 6 months to 10 years). However, one patient who presented with an ileal metastasis recently developed a second primary extragonadal mediastinal mixed germ-cell tumor with YST and embryonal carcinoma components and an elevated serum level of AFP (27,000 ng/ml) after a 10-year disease-free follow-up. This study strongly suggests that minor elevations (

Histologic variations in the epididymis: findings in 167 orchiectomy specimens.

Nonpathologic morphologic variations in the epididymal histology in 167 orchiectomy specimens were analyzed to assess and document the nature, frequency, and possible relation to patient age and underlying testicular pathology. Variations in histology included intranuclear eosinophilic inclusions, lipofuscin pigment, cribriform hyperplasia, Paneth cell-like metaplasia, and nuclear atypia. Intranuclear eosinophilic inclusions were observed in 72.5% of patients, and they appeared to occur at an older age than cribriform hyperplasia and Paneth cell-like metaplasia. Lipofuscin pigment was found in 32.9% of patients; this change was observed predominantly in ductuli efferentes and was more commonly associated with obstructive changes. Cribriform hyperplasia was seen in 41.9% of patients, and it occurred in 1 normal testis and in 33 testes with diverse pathologic alterations. Paneth cell-like metaplasia characterized by bright eosinophilic intracytoplasmic hyaline-like granules and globules, was present in 8.3% of patients and was accompanied by changes of obstruction in almost all instances. The globules were strongly periodic acid-Schiff positive, both before and after diastase digestion, and were negative for chromogranin A, KP-1, and MAC387 immunostains. Nuclear atypia, similar to that seen in seminal vesicles, was focally present in 13.8% of patients and tended to occur at an older age. The authors conclude that variations in epididymal morphology are fairly common and, therefore, surgical pathologists should be aware of these changes. Although exuberant in some patients, in no cases did these variations cause serious diagnostic problems.

Pseudomyxoma ovariilike posttherapeutic alteration in prostatic adenocarcinoma: a distinctive pattern in patients receiving neoadjuvant androgen ablation therapy.

Neoadjuvant combination endocrine therapy that uses leuprolide and flutamide may result in various histologic changes in nontumoral and cancerous prostatic tissues. Posttreatment pseudomyxoma ovariilike change in prostatic adenocarcinoma is a distinctive alteration that may be the only evidence of regressed tumor and can be potentially confused with mucinous carcinoma. We studied 53 clinically localized prostatic adenocarcinomas after 3 to 5 months of treatment with leuprolide and flutamide. Alterations in prostatic adenocarcinoma in posttreatment radical prostatectomy specimens were assessed and compared with pretreatment needle biopsies. All radical prostatectomy specimens exhibited previously well-characterized therapy-associated changes in benign and malignant elements. Thirteen (20%) cases exhibited a distinctive alteration not seen in pretreatment needle biopsies that consisted of minute to large pools of extravasated secretions that resembled pseudomyxoma ovarii and that dissected through prostatic stroma with an infiltrative appearance when viewed at low power. Associated recognizable tumor was present in 10 of 13 (77%) of these cases. Secretions were basophilic in routine sections and contained occasional degenerated cells. Rare pancytokeratin positive cells were seen at the secretion/stroma interface with uniformly negative staining for the high molecular weight keratin 34 beta E-12. The secretions were periodic acid-Schiff positive after diastase digestion and were mucicarminophilic and reactive with Alcian blue at a pH of 2.5. These foci comprised < 5% of the tumor in 5 cases and 5-40% in 5 cases. In 3 cases, 1-2 foci < 1.0 mm exhibited the pseudomyxoma ovariilike changes and were the only evidence of treated tumor. There was no correlation between the presence of pseudomyxomalike change and dose/duration of neoadjuvant therapy, postprostatectomy clinical follow-up, original or final Gleason pattern/score, or pathologic stage. Pseudomyxoma ovariilike change consists of extravasated acid mucin, lacks prostatic basal cells, often occurs in intimate association with residual prostatic adenocarcinoma in posttreatment radical prostatectomy specimens, and probably represents tumor regression as a result of tumor cell attrition secondary to androgen ablation.

Identification of HER-2/neu oncogene amplification by fluorescence in situ hybridization in stage I endometrial carcinoma.

Prognostic factors capable of detecting potential for aggressive disease in early stage endometrial cancer might be useful in selecting patients for early adjuvant therapy. Sixty-three patients with surgical Stage I endometrial carcinoma treated by hysterectomy with a mean follow-up of 55 months were evaluated for tumor type, grade, depth of myometrial invasion, presence of vascular invasion, DNA ploidy, and HER-2/neu overexpression by immunohistochemical techniques. These results were compared with HER-2/neu gene amplifications evaluated by fluorescence in situ hybridization (FISH) and their ability to predict disease survival. For FISH, sections 5 microns thick of formalin-fixed, paraffin-embedded tissues were processed using the Oncor Chromosome In Situ Hybridization System. Automated hybridization using the Ventana Gen was performed with the Oncor unique sequence digoxigenin-labeled HER-2/neu DNA probe. Gene copy numbers were evaluated using the Zeiss Axioskop50 fluorescence microscope. HER-2/neu amplification was noted in 24 (38%) of 63 cases. By multivariate analysis, only aneuploidy (P = .04) and HER-2/neu amplification by FISH (P = .04) independently correlated with survival. Although we saw a relationship between HER-2/neu protein expression and gene amplification, this trend did not achieve statistical significance. HER-2/neu oncogene amplification can be assessed using automated FISH on formalin-fixed, paraffin-embedded tissue. HER-2/ neu amplification predicts poor outcome in Stage I endometrial cancer. HER-2/neu amplification status has potential use in the identification of patients with high risk of disease recurrence who might benefit from intensified therapy.

Breast cancer in a man with human immunodeficiency virus infection.

Non-acquired immunodeficiency syndrome (AIDS)-defining neoplasms are being increasingly recognized in patients infected with the human immunodeficiency virus (HIV). The incidence of Hodgkin's disease and seminoma has recently been reported to be increasing in these patients. This article describes the second case of breast cancer in an HIV-infected male patient. A total of 11 cases of coincident breast cancer and HIV infection have previously been reported. It may be prudent to consider breast cancer in the differential diagnosis of an axillary mass in an HIV-infected patient.

Blastic transformation of hairy cell leukemia.

OBJECTIVE: To report blastic transformation of hairy cell leukemia, an uncommon lymphoproliferative disorder of B-cell lineage. DESIGN: Routine histology, cytochemistry, and ultrastructural analysis were used to study this case. Immunoperoxidase studies for leukocyte common antigen (CD45), pan B-cell marker L26 (CD20), and hairy cell leukemia marker DBA.44 were performed. In addition, cell surface marker analysis for CD19, CD20, CD5, CD25, CD11c, and kappa and lambda light chains by flow cytometry was performed. RESULTS: The patient presented with typical clinical, morphologic, cytochemical, immunophenotypic, and ultrastructural features of hairy cell leukemia. Following splenectomy and prior to institution of any other therapy, he developed a blastic lymphoproliferative malignancy with loss of tartrate-resistant acid phosphatase activity, expression of cell surface markers CD11c and CD25, and immunoreactivity for DBA.44. CONCLUSION: We believe this to be the first report of such a transformation and recommend that the differential diagnosis of blastic transformation of chronic lymphoproliferative disorders include such a possibility.

Chondromyxoid fibroma of paranasal sinuses: report of two cases presenting with nasal obstruction.

Chondromyxoid fibroma (CMF) is a rare, benign cartilaginous tumor that often occurs in the metaphyses of long bones. Tumors of the craniofacial bones are extremely rare and most often involve the mandible and the maxilla. This report presents the clinicopathological and radiological features of two unusual cases of CMF arising in the paranasal sinuses that presented with nasal obstruction. The tumors arose in the sphenoid and ethmoid sinuses and were treated by curettage and resection, respectively. One of the two patients was 20 days old, suggesting a possible congenital origin.

Endocervical type glands in urinary bladder: a clinicopathologic study of six cases.

The authors report six cases of glandular lesions made up of endocervical type glands in the urinary bladders of women aged 34 to 65 years (mean, 39 years). Two patients presented with dysuria, one with painless hematuria, one with complaints of pelvic discomfort and hematuria, and one with vaginal discharge. The sixth patient was asymptomatic, but on a routine gynecologic examination, a pelvic mass was found. On physical examination, three women had masses between the bladder and uterus. Four lesions were located in the posterior wall of the urinary bladder, one in the dome, and one in the trigone. Four patients underwent biopsy of the bladder lesion. One of these patients had undergone a hysterectomy 10 years earlier. One woman with a pelvic mass between the bladder and uterus underwent a hysterectomy, bilateral salpingo-oophorectomy, and partial cystectomy. The sixth patient had a transurethral resection of the bladder tumor and left oophorectomy. Histologically, all cases showed intermediate to large-sized irregularly shaped endocervical type glands in the muscularis propria of the urinary bladder. Some glands exhibited cystic dilatation and contained mucinous secretions. The glands elicited no desmoplastic tissue reaction. The intraluminal mucin frequently contained polymorphonuclear leukocytes. In all cases, the glands were lined by mucinous, tall, columnar cells and less commonly by flattened to cuboidal cells. Rare admixed ciliated cells were also observed. The lining epithelium was bland in five cases, but moderate nuclear atypia was seen in one case. Mitoses were not observed in any case. Associated lesions included endometrial type glands surrounded by elastotic stroma in one case, exuberant cystitis glandularis in one case, and a pseudodiverticulum of the bladder in one case. Review of the slides from the patient who had had a hysterectomy 10 years previously revealed endocervical adenocarcinoma in situ. Follow-up (mean = 30 months; range = 6 to 60 months) shows that all patients are alive and well, suggesting that the lesion is benign.

Spermatic cord contamination in testicular cancer.

It is not uncommon to find testicular germ-cell tumors in the spermatic cord. This may represent contamination or true involvement (vascular invasion or direct tumoral extension into the cord). A correct identification of the process has important clinical implications. In a review of 326 testicular germ-cell tumors, 79 (24.2%) revealed tumor in the spermatic cord. Of these 79, contamination was found in 57 (72.1%), true involvement in 15 (19%), and true involvement and contamination in 7 (8.9%). Spermatic cord contamination was seen most frequently with seminomas: 34 (24.1%) of 141 seminomas and 20 (15.4%) of 130 mixed germ-cell tumors. Eighteen of the 20 mixed germ-cell tumors contained an embryonal carcinoma component. True involvement was seen most frequently in embryonal carcinoma. Six (15.4%) of 39 pure embryonal carcinomas demonstrated true cord involvement. Six mixed germ-cell tumors with true cord involvement contained an embryonal carcinoma component. Distinguishing between true involvement of the spermatic cord and contamination can occasionally be problematic. Because true involvement, especially at the spermatic cord resection margin, identifies patients at a high risk for relapse, the problem of contamination caused by inadequate precautionary measures can be avoided by meticulous handling and processing of the specimens.

Increased bcl-2 protein levels in prostatic adenocarcinomas are not associated with rearrangements in the 2.8 kb major breakpoint region or with p53 protein accumulation.

bcl-2, an inhibitor of programmed cell death (apoptosis), is present in high levels in a subset of prostatic adenocarcinomas. In this study, 42 prostatic adenocarcinomas were analyzed to determine whether increased bcl-2 levels are associated with rearrangements in the 2.8-kb major breakpoint region, an association known to occur in certain follicular lymphomas featuring a t(14:18) translocation. Immunostaining for bcl-2 and p53 proteins was performed on formalin-fixed, paraffin-embedded tumor specimens using murine anti-human bcl-2 and p53 monoclonal antibodies in all 42 cases. Genomic DNA from paired frozen samples of each tumor was subjected to digestion with HindIII and EcoRI and the products analyzed on a Southern blot with a 2.8-kb-digoxigenin-labeled major breakpoint region probe. Comparisons between groups were evaluated with the Fisher exact test. Diffuse, strong cytoplasmic immunoreactivity for bcl-2 was present in the epithelial cells of tumor glands in 16 of 42 cases (38%), including 8 of 19 low grade (Gleason score 6 and below) and 8 of 23 high grade (Gleason score 7 and above) prostatic adenocarcinoma. Southern blotting demonstrated a normal 2.8-kb germline DNA fragment in every case, with no evidence of rearrangement. Nuclear p53 staining was present in 10 of 24 high grade and 0 of 18 low grade tumors (P < 0.001). Only four cases exhibited positivity for both bcl-2 and p53, and there was no association of bcl-2 positivity with co-expression of the p53 protein (P = 0.58). We conclude that aberrations in the function of either bcl-2 or p53 could possibly modify the apoptotic pathway resulting in the extended survival of tumor cells. Also, increased bcl-2 levels in prostatic adenocarcinomas occur in the absence of detectable rearrangements in the major breakpoint region.

Multivariate survival analysis of clinicopathologic features in surgical stage I endometrioid carcinoma including analysis of HER-2/neu expression.

OBJECTIVE: We previously described vascular invasion-associated changes, defined as the presence of vascular invasion or perivascular lymphocytic infiltrates, as key prognostic indicators in stage I endometrioid carcinoma. The current study was undertaken to examine the prognostic value of HER-2/neu expression in relation to other factors, including vascular invasion-associated changes, in surgical stage I endometrioid carcinoma. STUDY DESIGN: Seventy-one patients with surgical stage I endometrioid carcinoma treated by hysterectomy and followed up were randomly chosen for retrospective analysis of prognostic indicators including standard clincopathologic features, deoxyribonucleic acid ploidy, and HER-2/neu expression. The latter was examined by an objective computerized quantitative immunohistochemical system. RESULTS: By univariate analysis many factors were found to correlate with outcome, including age, tumor grade, depth of invasion, ploidy, HER-2/neu expression, and vascular invasion-associated changes. By multivariate analysis only vascular invasion-associated changes, aneuploidy, and HER-2/neu overexpression were found to independently correlate with survival. Stratification of patients on the basis of these three features revealed survival rates of 100%, 92%, and 60% when none, one, and two or three features were present, respectively. CONCLUSION: This study suggests that HER-2/neu expression correlated with outcome independent of other factors in endometrial carcinoma and may aid in estimating prognosis. The prognostic value of HER-2/neu overexpression independent of vascular invasion suggests that this factor may operate by increasing the ability of tumor cells to grow at a distal site once vascular invasion occurs.