Contrast-enhanced and unenhanced diffusion-weighted imaging of the breast at 3 T.

AIM: To evaluate the effect of intravenous gadolinium contrast agent on diffusion-weighted sequences and apparent diffusion coefficient (ADC) measurements at 3 T. MATERIALS AND METHODS: Sixty-two biopsy-proven breast lesions were included in this prospective study. Magnetic resonance imaging (MRI) was performed at 3 T, using four echo-planar diffusion-weighted sequences (7,100 ms repetition time, 84 ms echo time) with b-values of 0 and 850, and 0 and 1,000 s/mm2. The first pair of DWI sequences was taken before intravenous contrast medium injection. The second pair of sequences was taken 6.5 minutes after intravenous contrast medium administration (right after the dynamic T1 sequence). A freeform region of interest (ROI) was drawn inside the lesion excluding adjacent normal tissue, necrotic, or cystic components and ADC values were calculated. The paired samples t-test was used to assess differences between ADC measurements before and after intravenous contrast medium administration. Sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve were calculated for each diffusion sequence. RESULTS: Twenty-seven malignant and 35 benign lesions were analysed. Fifty-eight lesions were masses, and four lesions were non-mass-like enhancements (NMLEs). Two of the NMLEs were malignant, and two were benign lesions. The contrast-enhanced ADC measurements were lower than the unenhanced measurements on b=850 and 1,000 s/mm2 (p<0.05). The receiver operating characteristic (ROC) analysis displayed similar area under the curve values between the different diffusion sequences. CONCLUSION: The injection of intravenous contrast medium reduces ADC values; however, the effect of contrast medium is modest. Sensitivity and specificity are not significantly affected.

Development of malignant lymphoma after metal-on-metal hip replacement: a case report and review of the literature.

A number of previous studies have reported a potential risk of malignancy, particularly hematological malignancy, developing in patients receiving a metal-on-metal (MoM) hip replacement. We report a case of malignant lymphoma that arose in a patient who had an MoM hip arthroplasty complicated by development of a pseudotumour. The tumour was a B cell follicular lymphoma that involved lymph nodes and bone. Metal ions are known to have a genotoxic effect on lymphoid cells. Although epidemiological studies have not established that there is an increased risk of lymphoma associated with MoM implants, only a relatively short time period has elapsed since re-introduction of this type of implant and long-term follow-up of patients with MoM implants is indicated.

Articular cartilage status 2 years after arthroscopic ACL reconstruction in patients with or without concomitant meniscal surgery: evaluation with 3.0T MR imaging.

PURPOSE: To assess articular cartilage changes in the knee joint as detected on 3.0T MR imaging after 2-year follow-up in patients who underwent arthroscopic anterior cruciate ligament reconstruction (ACLR) with or without concomitant meniscal surgery. METHODS: A total of twenty-nine patients (mean age 30.3 ± 10 years), who underwent arthroscopic ACLR, received clinical and imaging follow-up at an average of 27.8 ± 4.8 months after surgery. Our patients were divided into two subgroups: eighteen patients with additional meniscal injuries at the time of arthroscopic ACLR who underwent meniscal surgery and eleven patients with intact menisci. The cartilage status of all knees at the time of arthroscopic ACLR was recorded. All patients underwent an MRI scan preoperatively and at follow-up with the same imaging protocol. Cartilage status of all knee compartments was evaluated at the time of follow-up by MR imaging and the ICRS classification. RESULTS: Deterioration of the cartilage status was found at all knee compartments of our study group, with respect to the number of cartilage defects. The cartilage of the lateral femoral condyle (LFC) was most severely affected, followed by patellar and medial femoral condyle (MFC) cartilage. A statistically significant relation was found between surgery of the medial meniscus and the development of new cartilage defects in LFC (p = 0.01) and MFC (p = 0.03) after adjusting for the site of meniscal surgery. The cartilage of LFC and the status of the medial meniscus were also found to be significantly related (p = 0.04). Partial meniscectomy was found to be associated with an increased incidence of new cartilage defects when compared to either meniscal repair or absence of meniscal surgery, although it was not statistically significant. CONCLUSION: Development of new cartilage lesions was evident after 2-year follow-up in patients with arthroscopic ACLR as detected by MR imaging. There was a multicompartmental pattern of cartilage involvement, and the lateral compartment was most severely affected. Partial meniscectomy at the time of arthroscopic ACLR could be suggested as an additional risk factor for the progression of chondral lesions. LEVEL OF EVIDENCE: Prospective comparative study, Level II.

Intraosseous hibernoma: a rare adipocytic bone tumour.

Hibernoma is a benign adipose tumour that contains foetal brown fat cells. We report a case of hibernoma arising in the left ischium of a 65-year-old female with a past history of ovarian carcinoma. The patient presented with a relatively short history of left sacral/hip pain. Radiologically, the lesion, which was large (5 cm) and sclerotic, had been stable for a number of years. Histologically, it was composed mainly of plump cells with foamy, multivacuolated cytoplasm. These cells showed no reaction for epithelial, melanoma or leucocyte markers but expressed FABP4/aP2 and S100, indicating that they were brown fat cells. There was no mitotic activity or nuclear pleomorphism and the lesion was diagnosed as a benign intraosseous hibernoma (IOH). IOH is a recently identified benign adipocytic lesion that presents typically as a sclerotic bone lesion. It has characteristic morphological and immunophenotypic features and should be regarded as a discrete primary bone tumour that needs to be distinguished from metastatic carcinoma/melanoma, chondrosarcoma and metabolic storage diseases containing numerous foamy macrophages.

Primary synovial chondromatosis: a reassessment of malignant potential in 155 cases.

OBJECTIVE: Primary synovial chondromatosis (PSC) is a rare disorder characterised by cartilage formation in synovium-lined joints, tendon sheaths and bursae. It is thought that PSC cartilage arises from the proliferation of mesenchymal cells, which exhibit cartilaginous metaplasia in subintimal connective tissue. There are reports of transformation of PSC to chondrosarcoma, although the precise incidence and nature of this complication is uncertain. In this study we carried out a retrospective review PSC to determine the incidence of sarcomatous change in this condition, in addition to the clinical, radiological and pathological features that characterise this complication MATERIALS AND METHODS: We reviewed 155 cases of PSC and identified 4 cases (3 in the hip joint; 1 in the elbow joint) of aggressive behaviour and chondrosarcoma-like histology. RESULTS: Radiologically, these cases were all reported as showing features consistent with PSC and aggressive extra-articular soft tissue/bone involvement. Histologically, in addition to typical features of PSC, there was morphological evidence of peri-articular soft tissue and, in 2 cases, bone involvement by an infiltrating cartilaginous tumour. These tumours all behaved as locally aggressive neoplasms and did not give rise to metastasis. CONCLUSION: Our findings show that chondrosarcoma arises infrequently in PSC (approximately 2.5 %), and that this complication occurs most commonly in the hip joint (approximately 11 % of cases of hip PSC). These tumours behaved mainly as low-grade, locally aggressive tumours analogous to atypical cartilaginous tumour of bone/grade 1 chondrosarcoma of bone.

Elimination of motion and pulsation artifacts using BLADE sequences in shoulder MR imaging.

OBJECTIVES: To evaluate the ability of proton-density with fat-suppression BLADE (proprietary name for periodically rotated overlapping parallel lines with enhanced reconstruction in MR systems from Siemens Healthcare, PDFS BLADE) and turbo inversion recovery magnitude-BLADE (TIRM BLADE) sequences to reduce motion and pulsation artifacts in shoulder magnetic resonance examinations. MATERIALS AND METHODS: Forty-one consecutive patients who had been routinely scanned for shoulder examination participated in the study. The following pairs of sequences with and without BLADE were compared: (a) Oblique coronal proton-density sequence with fat saturation of 25 patients and (b) oblique sagittal T2 TIRM-weighed sequence of 20 patients. Qualitative analysis was performed by two experienced radiologists. Image motion and pulsation artifacts were also evaluated. RESULTS: In oblique coronal PDFS BLADE sequences, motion artifacts have been significantly eliminated, even in five cases of non-diagnostic value with conventional imaging. Similarly, in oblique sagittal T2 TIRM BLADE sequences, image quality has been improved, even in six cases of non-diagnostic value with conventional imaging. Furthermore, flow artifacts have been improved in more than 80% of all the cases. CONCLUSIONS: The use of BLADE sequences is recommended in shoulder imaging, especially in uncooperative patients because it effectively eliminates motion and pulsation artifacts.

Celiomesenteric trunk demonstrated by multi-detector computed tomography angiography: two cases of a rare vascular variation.

We present two cases of patients with celiomesenteric trunk in whom the celiac trunk and the superior mesenteric artery arise off a common vessel from the ventral part of the aorta, which was demonstrated by multi-detector (16 slices) computed tomography angiography (MDCTA) and confirmed by digital subtraction angiography (DSA). This is a very rare congenital vascular anomaly and its imaging demonstration is of great importance in several interventional procedures. These cases demonstrate the capability of MDCTA in the evaluation of abdominal aorta and its branches and shows that this method might replace diagnostic DSA.

Ultrasonographic evidence of inflammation is frequent in hands of patients with erosive osteoarthritis.

OBJECTIVE: Erosive osteoarthritis (OA) (EOA) is considered an aggressive form of primary OA that is defined radiographically by intra-articular erosions of the inter-phalangeal joints of the hand and characteristic deformities. The aim of the present study was the sonographic investigation of hand small joints in patients with EOA and comparison of the imaging findings with conventional radiography (CR). METHOD: Twenty-two patients (20 women, mean age 62.5 years) with clinical and radiographic diagnosis of EOA formed our study group. A total of 660 joints were assessed by both radiographs and ultrasound (US). US and plain films were evaluated by two different physicians on a blinded fashion. Erosions, osteophytes and deformities were evaluated by both US and plain films. Synovial thickening, effusion, and power Doppler signal indicative of abnormal vascularity were recorded in each joint during US scanning. RESULTS: Erosions were detected in 231/660 (35%) small joints by US and in 115/660 (17.4%) small joints by conventional radiographs (P<0.05). Osteophytes were detected in 360/660 (54.5%) small joints by US, and in 310/660 (47.0%) small joints by conventional radiographs (P<0.05). Thickened synovium was detected in 19 of 22 patients and increased intra-articular power Doppler signal, indicative of active inflammation, was detected in 18 of 22 patients. Thickened synovium was found in 159/660 (24.1%), effusion in 119/660 (18%) and increased power Doppler in 148/660 (22.4%) small joints. Intra-observer kappa value for agreement regarding US was 0.81 and plain films 0.86. In 31 instances extensive finger tenosynovitis was also evident. CONCLUSION: In patients with EOA, US is a reliable and a more sensitive imaging modality than CR in detecting erosions and osteophytes. US detects inflammatory changes in small hand joints in the vast majority of patients with EOA and suggests that current treatment modalities are inadequate treatment for this disease.

Symptomatic partial rotator cuff tears: diagnostic performance of ultrasound and magnetic resonance imaging with surgical correlation.

BACKGROUND: The painful shoulder is a relatively common clinical entity that may be attributed to a variety of pathologies, including partial rotator cuff tears. Conservative treatment or surgical intervention may be offered, depending on the extent of the partial tear and the degree of patient discomfort. PURPOSE: To apply ultrasound (US) imaging in order to evaluate the prevalence of partial rotator cuff tears in patients with painful shoulders. MATERIAL AND METHODS: Fifty-six patients (17 men, 39 women; mean age 53.7 years) were included in the study, with symptomatic impingement syndrome of the shoulder after having failed to respond to conservative treatment. All patients underwent US and magnetic resonance imaging (MRI) scans prior to surgical intervention. RESULTS: Arthroscopy or mini-open surgery revealed 53 cases with partial tears of the rotator cuff and three with extensive tendinopathy. Both imaging modalities detected successfully 44 cases of partial tears of the supraspinatus tendon. US imaging yielded a sensitivity of 95.6%, a specificity of 70%, an accuracy of 91%, and a positive predictive accuracy of 93.6%. The corresponding values for MRI were 97.7%, 63.6%, 91%, and 91.7%, respectively. CONCLUSION: US imaging can be considered almost equally effective in detecting partial tears of the rotator cuff compared to MRI, particularly located in the area of the supraspinatus tendon. MRI may be reserved for doubtful or complex cases, in which delineation of adjacent structures is mandatory prior to surgical intervention.

Necrotic granulomatous pseudotumours in bilateral resurfacing hip arthoplasties: evidence for a type IV immune response.

Clinical, radiological and histological findings were analysed in four patients who developed bilateral pseudotumours following metal-on-metal (MoM) resurfacing arthroplasties of both hips. Using a panel of monoclonal antibodies directed against HLA-DR, macrophages (CD14, CD68), dendritic cells (DC-SIGN, S100, CD11c), B cells (CD20), and T cells (CD3, CD4, CD8), the nature of the heavy inflammatory response seen in these cases was examined. Bilateral masses developed in periprosthetic soft tissues following the second MoM arthroplasty; these were characterised histologically by extensive coagulative necrosis, a heavy macrophage infiltrate and the presence of granulomas containing macrophages and giant cells; there was also a diffuse lymphocyte and variable plasma cell and eosinophil polymorph infiltrate. Immunohistochemistry showed strong expression of HLA-DR, CD14 and CD68 in both granulomatous and necrotic areas; lymphocytes were predominantly CD3+/CD4+ T cells. The clinical, morphological and immunophenotypic features of these necrotic granulomatous pseudotumours, which in all cases develop following a second resurfacing hip arthroplasty, is suggestive of a type IV immune response, possibly to MoM metal alloy components.

Radiological and pathological diagnosis of paediatric bone tumours and tumour-like lesions.

Primary bone tumours are rare but account for a significant proportion of cancers occurring in childhood and adolescence. Malignant bone tumours need to be distinguished not only from their benign counterparts but also from tumour-like lesions, many of which are developmental or reactive in nature and are found commonly in the paediatric population. Taking note of the age of the patient and the site of the lesion within bone (aided by several imaging techniques including plain radiographs, ultrasound, computed tomography, bone scintigraphy and magnetic resonance imaging) is essential for pathological diagnosis. Immunohistochemistry, cytogenetics, molecular analysis and other techniques are now powerful diagnostic tools in bone pathology. This review aims to provide an approach to the radiological and pathological diagnosis of paediatric bone tumours. It also provides a brief overview of some of the more common bone tumours and tumour-like lesions, both benign and malignant, which occur in childhood and adolescence.

Radiation dose optimisation and risk estimation to patients and staff during hysterosalpingography.

Hysterosalpingography (HSG) is an efficient radiological examination for the evaluation of the female reproductive tract. However, it involves unavoidable irradiation to the ovaries of women in childbearing age. Therefore, radiation dose optimisation is required in order to reduce the probability of the associated risks. This study attempts to: measure patient and staff doses, estimate the effective dose and radiation risk for HSG using digital fluoroscopic images. Thirty-seven patients with infertility were examined using two digital X-ray machines. Thermoluminescence dosimeters (TLD) were used to measure entrance surface dose (ESD) for patients and staff during the procedure. The mean ESD and thyroid surface dose of the patient were 3.60 and 0.17 mGy, respectively, while the mean ESD for the staff was 0.18 mGy per procedure. The patient overall risk for cancer and hereditary effects is 24 x 10(-6), while the risk for the staff is negligible. HSG with fluoroscopic technique demonstrate improved dose characteristics, compared to the conventional radiographic-based technique, reducing the surface dose by a factor of 3, without compromising the diagnostic findings.

Primary intraosseous meningioma: an osteosclerotic bone tumour mimicking malignancy.

BACKGROUND: Sclerotic tumours of the calvarial bones are rare and may be due to primary and secondary bone tumours as well as extradural tumours of meningeal origin. CASE PRESENTATION: We report a case of primary intraosseous meningioma (PIM) which arose in the frontal bone of a 63 year old woman who complained of progressive pain and thickening of the right skull. Radiology showed a large osteosclerotic lesion in the right frontal bone. Histology showed an intraosseous lesion containing dense fibrous tissue in which there were scattered cells that expressed epithelial membrane antigen and progesterone receptor. The tumour was partially resected and 3 years after operation has not recurred. CONCLUSIONS: PIM is a rare tumour which needs to be distinguished from primary/secondary osteosclerotic calvarial bone tumours.

High resolution computed tomography findings on the lung of early breast-cancer patients treated by postoperative breast irradiation with a hypofractionated radiotherapy schedule.

CONTEXT: Hypofractionated breast radiotherapy (RT), although convenient for patients and health care systems, could have a negative impact on normal tissues such as lung. AIMS: To evaluate radiation-induced lung toxicity in early breast-cancer patients treated by hypofractionated RT. SETTINGS AND DESIGN: We have been using the 42.5 Gy/16 fractions RT schedule since May 2003. As large fraction size is related to increased normal tissue toxicity we intended to investigate the possible radiation-induced lung toxicity to these patients, by performing high-resolution computed tomography (HRCT) 6 months after the completion of the treatment. METHODS AND MATERIAL: A group of 30 consecutive early breast cancer patients (T1-2N0M0) have been treated by the above-mentioned RT schedule, using a pair of opposing tangential fields. The impact of chemotherapy and hormonotherapy and various breast size-related parameters on HRCT lung changes were investigated. Acute skin and breast tissue reactions were also recorded. STATISTICAL ANALYSIS USED: Correlation of numerical variables was investigated by Pearson correlation coefficient. Logistic regression analysis was used to investigate correlation between HRCT findings (present vs absent) with other variables. RESULTS: Minimal HRCT findings were evident in 15/30 patients. These included small septal lines, linear and subpleural opacities and to a lesser extend, focal-ground glass opacification. The HRCT findings were positively correlated only to field separation (distance between the entrance points of the tangential beams on the breast) (H.R.=1.33, 95% CI: 1.013-1.75). CONCLUSIONS: The short 16-fraction RT schedule for early breast-cancer patients appears to have a minor effect on the underlying lung parenchyma.

RhBMP-7 for the treatment of nonunion of fractures of long bones.

We report the outcome of 84 nonunions involving long bones which were treated with rhBMP-7, in 84 patients (60 men: 24 women) with a mean age 46 years (18 to 81) between 2003 and 2011. The patients had undergone a mean of three previous operations (one to 11) for nonunion which had been present for a mean of 17 months (4 months to 20 years). The nonunions involved the lower limb in 71 patients and the remainder involved the upper limb. A total of 30 nonunions were septic. Treatment was considered successful when the nonunion healed without additional procedures. The relationship between successful union and the time to union was investigated and various factors including age and gender, the nature of the nonunion (location, size, type, chronicity, previous procedures, infection, the condition of the soft tissues) and type of index procedure (revision of fixation, type of graft, amount of rhBMP-7) were analysed. The improvement of the patients' quality of life was estimated using the Short Form (SF) 12 score. A total of 68 nonunions (80.9%) healed with no need for further procedures at a mean of 5.4 months (3 to 10) post-operatively. Multivariate logistic regression analysis of the factors affecting union suggested that only infection significantly affected the rate of union (p = 0.004).Time to union was only affected by the number of previous failed procedures (p = 0.006). An improvement of 79% and 32.2% in SF-12 physical and mental score, respectively, was noted within the first post-operative year. Rh-BMP-7 combined with bone grafts, enabled healing of the nonunion and improved quality of life in about 80% of patients. Aseptic nonunions were much more likely to unite than septic ones. The number of previous failed operations significantly delayed the time to union.

Expression of cyclin D3 and cyclin E and identification of distinct clusters of proliferation and apoptosis in diffuse large B-cell lymphomas.

In the present study 79 cases of de novo Diffuse Large B-cell Lymphomas (DLBCL) were studied in order: a) to analyse the expression of cyclin D3, cyclin E and cyclin D1 in relation to other proliferative features (expression of Ki67, cyclin A and cyclin B1), the apoptosis status and the expression of p53, Rb, p16 and p27; and b) to determine whether distinct clusters of proliferation and apoptosis could be identified in DLBCL. Overexpression of cyclin D3 and cyclin E was found in 35/79 (43%) and 18/79 (22%) cases, respectively, whereas overexpression of cyclin D1 was not detected in any case. In most cases (39/46) overexpression of cyclin D3 and cyclin E was mutually exclusive possibly reflecting different underlying pathways inducing deregulated expression of these cyclins. In most cases (29/35) overexpression of cyclin D3 was mutually exclusive with Rb/p16 aberrant expression status supporting an oncogenic role for cyclin D3 and suggesting that the pathogenetic effect of cyclin D3 overexpression occurs through perturbation of the Rb1 pathway. Combined alterations of the P53 and the Rb/p16/cyclin D3 expression status were significantly associated with higher mean values of cyclin A (p=0.023) and cyclin B1 (p=0.033) indicating that concurrent impairment of the p53 and Rb1 pathways induces increased tumour cell proliferation in DLBCL. Cluster analysis of the apoptosis and the proliferation status permitted separation of DLBCL into distinct groups with low (44 cases) and high (18 cases) apoptotic activity and into distinct groups with low (32 cases), intermediate (36 cases) and high (11 cases) proliferative activity. The identification of distinct clusters with respect to the proliferation and the apoptosis status indicates that groups with distinct cellular kinetic properties can be defined in the histological group of DLBCL.

Cytotoxic protein expression in non-Hodgkin's lymphomas and Hodgkin's disease.

Recent studies have shown that some peripheral T-cell lymphomas (PTCL) could be derived from lymphocytes with cytotoxic potential. Therefore, we have investigated by immunohistochemistry 34 cases of PTCL including 2 cases of hepatosplenic gamma delta PTCL and 5 cases of sinonasal NK-cell lymphomas as well as 7 cases of T-lymphoblastic lymphomas (T-LBL) for the expression of the cytotoxic proteins TIA-1 and granzyme B. In addition, 50 cases of Hodgkin's disease (HD) were investigated in order to see if these cytotoxic proteins are expressed by Hodgkin and Reed-Sternberg (HRS) cells. Expression of the TIA-1 is characteristic of cytotoxic cells regardless of their activation status whereas expression of granzymes is highly increased in activated cytotoxic cells. All the five cases of sinonasal NK-cell lymphomas expressed TIA-1 and granzyme B in most tumour cells. The two gamma delta PTCL cases expressed TIA-1 protein in most tumour cells but not granzyme B. Of the 32 other PTCL, 9 cases showed cytotoxic protein expression in tumour cells. These cases comprised 2 pleomorphic medium large cell (PML) (1 nodal and 1 intestinal) and 7 CD30 positive anaplastic large cell lymphomas (ALCL) (5 nodal and 2 cutaneous). Cytotoxic protein expression in our series appeared to be related to the location since 10/18 (55%) extranodal PTCL and NK-NHL and only 6/21 (28%) nodal PTCL expressed TIA-1, and related to histology since, in nodal PTCL, this pattern was observed in most anaplastic (5/6 cases) and in a few pleomorphic (1/9 cases) lymphomas, but not in AILD-type NHL (0/6 cases). The 7 cases of T-LBL did not express cytotoxic proteins in tumour cells. EBV was detected by EBER RNA in situ hybridization (RISH) in tumour cells in all 5 sinonasal NK-NHL and in scattered atypical cells in all 6 cases of AILD. Two of the 50 cases of HD weakly expressed TIA-1 and granzyme B in a proportion of HRS cells. EBV was detected by RISH in 19/50 cases of HD but no correlation was found between EBV status and expression of cytotoxic proteins in HRS cells. However, the finding that granzyme B positive cells were found very rarely in close vicinity of HRS cells suggests that the function of activated cytotoxic cells is locally inhibited by the HRS cells and/or the reactive cells in the vicinity of HRS cells. Taken together our data suggest that: a) sinonasal NK-cell NHL represent tumours of activated cytotoxic NK-cells, b) the hepatosplenic gamma delta PTCL represent tumours of nonactivated cytotoxic gamma delta T-cells, c) a small proportion of other PTCL, mostly anaplastic large cell lymphomas represent tumours of cytotoxic T-cells and d) only very few cases of HD expressing cytotoxic proteins in a proportion of tumour cells, could be derived from activated cytotoxic cells.

Immunohistochemical detection of bcl2, p53, mdm2 and p21/waf1 proteins in small-cell lung carcinomas.

Thirty-one cases of small cell lung carcinomas (SCLC) were investigated by immunohistochemistry for the expression of bcl-2. P53 and the wild-type (wt) p53-induced proteins mdm2 and p21/waf1. Bcl-2 protein was detected in 24/31 cases of SCLC(77%) and p53 protein in 13/31 cases (42%). No correlation was found between histological subtype of SCLC and bcl-2 or p53 expression. Comparison between bcl-2 and p53 expression showed that 14/31 cases (45%) were only bcl-2 positive, 3/31 (11%) were only p53 positive, 10/31 (32%) were positive for both proteins and 4/31 (13%) were negative for both proteins. Mdm2 protein was detected in 2/32 SCLC which were also p53 positive. P21 protein was detected in 6/32 SCLC. Four of the p21 positive SCLC were negative for both p53 and mdm2, and two were positive for both p53 and mdm2 proteins. The significant expression of bcl-2 protein in SCLC suggests that bcl-2 may be involved in the pathogenesis of most SCLC by inhibiting apoptosis during neoplastic transformation. The expression of p53 protein in SCLC is likely to be related to underlying p53 gene mutations since these genetic alterations are very frequent in SCLC. This can be supported by our findings that 11/13 p53 positive SCLC were mdm2 and p21 negative. The two cases with p53+/mdm2+/p21+ phenotype may represent tumours with wt p53 gene and p53 protein immunoexpression due to binding to mdm2 protein. The four cases with p53-/mdm2-/p21+ phenotype may represent tumours with p53-independent p21 protein expression. Coexpression of p53 and bcl-2 proteins in a proportion of SCLC suggests that in these tumours p53 does not maintain its suppressive effect on bcl-2 expression as has been reported in vitro. Further studies at the DNA and RNA level are required to clarify the involvement of bcl-2, p53, mdm2 and wafl genes in SCLC pathogenesis.

Expression of p53, p21, mdm2, Rb, bax and Ki67 proteins in lymphomas of the mucosa-associated lymphoid (MALT) tissue.

We have investigated by immunohistochemistry 38 cases of B-cell MALT-NHL comprising 23 high grade (HG) and 15 low grade-(LG) tumours for the expression of p53, mdm2, p21, Rb, Ki67, bcl2 and Bax proteins. P53, mdm2 and p21 proteins were found in at least 5% of the tumour cells in 13/23, 2/23 and 11/23 HG tumours, respectively. These proteins were detected in very rare tumour cells in LG tumours. The following patterns were recorded in HG tumours: p53+/p21+/mdm2+ (2 cases), p53+/p21+/mdm2- (7 cases), p53+/p21-/mdm2- (4 cases), p53-/p21-/mdm2- (18 cases) and p53-/p21+/mdm2-(2 cases). Proliferative Ki67 index and Rb protein expression were higher in HG than in LG MALT-NHL. Bcl2 protein was expressed in all LG MALT-NHL, whereas only 2/23 HG MALT-NHL were bcl2 positive in most tumour cells. Bax protein was expressed in all MALT-NHL with HG tumours being positive in higher proportion of tumour cells than LG tumours. These findings show that significant expression of p53, mdm2, p21,Ki67 and Rb proteins occurs more frequently in aggressive histotypes of MALT-NHL. The parallel Rb/Ki67 expression suggests that Rb protein expression in MALT-NHL is normally regulated in relation to the proliferative growth fraction of the tumours. The pattern p53+/p21+/mdm2 +/- may represent MALT-NHL with wild type (wt) p53 gene since mdm2 and p21 proteins are inducible by wt p53 gene. The pattern p53+/mdm2-/p21-may represent MALT-NHL with p53 gene mutations unable to activate expression of mdm2 and p21 proteins. MALT-NHL with the p53-/mdm2-/p21 + pattern may be consistent with p53-independent p21 expression. Bax protein expression in all MALT-NHL suggests a role for this protein in the pathogenesis of these tumours.

Immunohistochemical detection of bcl2, p53, mdm2 and p21/waf1 proteins in small-cell lung carcinomas.

Thirty-one cases of small cell lung carcinomas (SCLC) were investigated by immunohistochemistry for the expression of bcl-2, p53 and the wild-type (wt) p53- induced proteins mdm2 and p21/waf1. Bcl-2 protein was detected in 24/31 cases of SCLC(77%) and p53 protein in 13/31 cases (42%). No correlation was found between histological subtype of SCLC and bcl-2 or p53 expression. Comparison between bcl-2 and p53 expression showed that 14/31 cases (45%) were only bcl-2 positive, 3/31 (11%) were only p53 positive, 10/31 (32%) were positive for both proteins and 4/31 (13%) were negative for both proteins. Mdm2 protein was detected in 2/32 SCLC which were also p53 positive. P21 protein was detected in 6/32 SCLC. Four of the p21 positive SCLC were negative for both p53 and mdm2, and two were positive for both p53 and mdm2 proteins. The significant expression of bcl-2 protein in SCLC suggests that bcl-2 may be involved in the pathogenesis of most SCLC by inhibiting apoptosis during neoplastic transformation. The expression of p53 protein in SCLC is likely to be related to underlying p53 gene mutations since these genetic alterations are very frequent in SCLC. This can be supported by our findings that 11/13 p53 positive SCLC were mdm2 and p21 negative. The two cases with p53+/mdm2+/p21+ phenotype may represent tumours with wt p53 gene and p53 protein immunoexpression due to binding to mdm2 protein. The four cases with p53-/mdm2-/p21+ phenotype may represent tumours with p53-independent p21 protein expression. Coexpression of p53 and bcl-2 proteins in a proportion of SCLC suggests that in these tumours p53 doses not maintain its suppressive effect on bcl-2 expression as it has been reported in vitro. Further studies at DNA and RNA level are required to clarify the involvement of bcl-2, p53, mdm2 and waf1 genes in SCLC pathogenesis.