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STRA13 expression and subcellular localisation in normal and tumour tissues: implications for use as a diagnostic and differentiation marker.

BACKGROUND: STRA13 is a bHLH transcription factor that plays a crucial role in cell differentiation, proliferation, apoptosis, and response to hypoxia. OBJECTIVE: To assess STRA13 involvement in carcinogenesis and evaluate its diagnostic value. METHODS: A comprehensive analysis was undertaken of the endogenous protein expression in 389 normal and corresponding malignant specimens, using newly generated polyclonal antibodies. RESULTS: STRA13 was commonly expressed in epithelial cells of normal and neoplastic tissues where it was confined mostly to the nucleus. Intense cytoplasmic STRA13 immunoreactivity was characteristic of myoepithelial and differentiated squamous epithelial cells of all organ sites and their neoplastic counterparts, suggesting application of STRA13 as a myoepithelial cell marker. A distinctive apical granular cytoplasmic staining pattern observed in the pancreas and large intestine was retained in corresponding metastatic carcinomas, providing for identification of the primary sites of these disseminating tumours. In less differentiated tumours there was a tendency to lose the cytoplasmic staining or to switch to nuclear STRA13 staining. Analysis of STRA13, HIF-1alpha, and CAIX expression patterns in a large set of various tumours substantiated the association of STRA13 with HIF-1alpha expression and hypoxia in vivo. Investigation of the molecular mechanisms of STRA13 nucleo-cytoplasmic shuttling suggested that STRA13 employs nuclear import/export that utilises the NLS/NES motifs situated within the N-terminus and in the middle of the protein. CONCLUSIONS: STRA13 may serve as a marker for myoepithelial cells, for the degree of tumour differentiation, and for identification of the primary site of certain metastatic tumours. In combination with CAIX and CAXII markers, it may lead to a more accurate classification of all renal carcinomas.

Antibody Specificity↗

Sequential intrahepatic fluorodeoxyuridine and systemic fluorouracil plus leucovorin for the treatment of metastatic colorectal cancer confined to the liver.

PURPOSE: Extrahepatic metastasis represents a frequent pattern of disease progression when fluorodeoxyuridine (FUDR) is given by the intraarterial route for the treatment of unresectable colorectal liver metastases. Systemic fluorouracil (5-FU) plus leucovorin was added to intrahepatic FUDR to prolong the duration of disease control. METHODS: Only patients with colorectal cancer who had evidence of unresectable metastases confined to the liver were eligible. Laparotomy was performed to establish arterial perfusion of the liver. Cycles of intrahepatic FUDR followed by a 1-week rest period then intravenous chemotherapy with 5-FU plus leucovorin were administered until maximal regression of hepatic metastases. Maintenance chemotherapy with 5-FU plus leucovorin was then given until disease progression. RESULTS: Fifty-seven patients entered this trial; four patients (7%) were ineligible and 13 (23%) did not receive any chemotherapy on study because of findings at laparotomy. The 40 eligible patients who began chemotherapy are included in the statistical analyses. Twenty-five patients (62% of those who received chemotherapy) experienced regression of liver metastases. The median time to tumor progression was 9 months, but only 3% remained progression-free at 24 months. The median survival duration was 18 months. Toxicity was tolerable with no cases of biliary sclerosis. One treatment-related fatality due to sepsis was observed. CONCLUSION: Although short-term treatment results appear to be somewhat better than we have previously observed with intrahepatic FUDR alone, the sequential regimen did not have an impact on long-term, progression-free survival in patients with unresectable liver metastases. We are now investigating this regimen as surgical adjuvant therapy in selected patients following hepatic metastasectomy where this aggressive approach might have a greater therapeutic effect in the minimal residual disease setting.

Adult↗

Identifying colorectal metastases in liver biopsies: the novel CDX2 antibody is less specific than the cytokeratin 20+/7- phenotype.

BACKGROUND: Immunohistochemistry plays an important role in tracing the primary site in metastatic tumors of unknown origin. Therefore, determining the cytokeratin (CK) 20/CK7 pattern of metastases is one of the most helpful procedures as the CK20+/CK7- pattern is typical of colorectal adenocarcinomas. Expression of CDX2 protein is a new, highly specific and sensitive marker of the intestinal origin of adenocarcinomas. In the present study we compared the sensitivity and specificity of CDX2 expression and the CK20+/CK7- phenotype in predicting the colorectal origin of liver metastases. MATERIAL/METHODS: The study was carried out on a consecutive series of 125 core-needle biopsies of metastatic adenocarcinomas of the liver. Most of the patients were followed up to death, and primary tumor localization could be established in 102 cases by a combination of clinical, radiological, histological and, in some cases, autopsy data. All the needle biopsies were immunohistochemically stained for CK7, CK20 and CDX2. CDX2 expression (at 10% and 50% cut-off levels) and the CK20/CK7 pattern of the metastases were correlated to the primary site established. RESULTS: The CK20+/CK7- pattern showed a specificity of 98.7% in predicting colorectal primary localization, which was superior to that of CDX2 expression at both cut-off levels (90% and 95.3% respectively). The sensitivity of CDX2 expression in these circumstances was 84% at the 10% cut-off, somewhat higher than that of the CK20+/CK7- phenotype (79.5%), but lower at the 50% cut-off level (72.7%). CONCLUSIONS: The CK20+/CK7- immunophenotype is more specific in predicting the colorectal origin of liver metastasis than CDX2 expression.

Adenocarcinoma↗

The distribution of lectin receptor sites in human breast lesions.

Conflicting data regarding the status of A, B, H and T antigens in epithelium of normal, mastopathies, fibroadenomas and carcinomas of the breast stimulated us to re-examine the carbohydrate residues in these condition. Currently, we extended the number of carbohydrate residues studied by using ten different biotinylated lectins as probes and avidin-biotin-peroxidase complex (ABC) as a visualant. In addition, the pattern of lectin staining of cancerous cells in primary and metastatic sites was compared. In primary and metastatic breast carcinomas, lectin receptor sites were stained more intensely with Concanavalia ensiformi agglutinin (*Con A), Ricinus communis agglutinin-I (RCA-I) and wheat germ agglutinin (WGA), than in normal breast, in mastopathies or in fibroadenomas. Cryptic receptor sites for peanut agglutinin (PNA) were stained in all cases of breast carcinomas, while free PNA sites stained only in a few cases of well-differentiated carcinomas. Receptors sites for Ulex europaeus agglutinin-I (UEA-I) stained non-malignant epithelium of patients with blood group H but did not stain malignant cells. The results show significant differences in lectin-binding patterns and staining intensities between normal and non-malignant, and malignant epithelial breast cells. Furthermore, these results indicate that in malignant cells, there is an increased content of sialic acid-rich carbohydrates but not of asialylated glycoconjugates.

Adenofibroma↗

Non-homogeneity of serum alkaline phosphatase activity in certain diseases of the liver and bile ducts investigated by polyacrylamide electrophoresis.

In 47 patients with hepatocellular or obstructive jaundice and 20 healthy controls the alkaline phosphatase isoenzyme pattern was determined by means of electrophoresis on polyacrylamide gel. It was demonstrated that the main activity of alkaline phosphatase (AP) in healthy subjects was connected with beta globulins while beta lipoproteins contained only traces of this activity. In hepatocellular jaundice during viral hepatitis only a slight rise was found of the activities of isoenzymes present in healthy subjects, and no zones of additional activity were found. In obstructive jaundice of benign as well malignant etiology the beta lipoprotein zone increased also significantly, moreover an additional activity zone was revealed moving in the gel together with alpha2macroglobulins. In 40% of cases of obstructive jaundice caused by metastatic malignant neoplasms in the liver a 4-fraction isoenzyme pattern of AP was demonstrated with additional activity in the haptoglobin zone.

Adult↗

Diagnostic utility of renal cell carcinoma marker in cytopathology.

Renal cell carcinoma (RCC) not uncommonly presents with metastases and causes diagnostic difficulty to the cytopathologist who is involved in the initial diagnostic workup of tumors with an unknown primary site. RCC marker (RCC Ma) recognizes a human proximal tubule antigen and was shown to have high specificity and relatively low sensitivity in preliminary studies on routinely processed tissue sections. We investigated the diagnostic usefulness of RCC Ma immunohistochemically in fine-needle aspiration (FNA) samples. A total of 34 FNA samples obtained from the following carcinomas were used: 7 RCCs, 5 metastatic RCCs, 4 hepatocellular carcinomas, 2 non-small cell carcinomas of the lung, 3 metastatic non-small cell carcinomas of the lung, 4 invasive ductal carcinomas of the breast, 2 pancreatic ductal adenocarcinomas, 4 metastatic transitional cell carcinomas of the urinary bladder, and 3 metastatic colon carcinomas. Routinely processed cell block sections of FNA specimens were stained with RCC Ma by using routine immunohistochemistry. Presence and distribution of staining were evaluated. Two of 7 (29%) primary and 2 of 5 (40%) metastatic RCCs showed immunoreactivity in less than 50% of carcinoma cells. Staining was focal, cytoplasmic, and granular. Scattered positive cells were present in two of the four hepatocellular carcinomas. All breast, lung, pancreas, colon, and transitional cell carcinomas were negative. RCC antibody has a low sensitivity (33%), most likely because of its focal staining pattern, and a high specificity (91%) in FNA specimens. Immunoreactivity in metastatic carcinoma of an unknown primary site, especially as part of a panel of antibodies, is useful in diagnostic cytopathology. RCC antibody has not been studied in hepatocellular carcinoma, and the significance of positivity observed in some of our cases is unclear.

Antibodies, Monoclonal↗

Bloodborne metastatic tumors to the gastrointestinal tract: CT findings with clinicopathologic correlation.

OBJECTIVE: In this essay, we illustrate the CT features of bloodborne metastases to the gastrointestinal tract from various malignancies with an emphasis on clinicopathologic correlation. CONCLUSION: Familiarity with CT findings of bloodborne metastases to the gastrointestinal tract and an understanding of the disease spread pattern in common primary cancers will be helpful not only in detecting metastatic disease but also in minimizing the possibility of mistaking metastasis for another metachronous malignancy.

Adult↗

Prognostic factors and imaging patterns of recurrent pulmonary nodules after thoracotomy in children with osteosarcoma.

BACKGROUND: In children with osteosarcoma who have undergone thoracotomy, it often is difficult to distinguish metastatic from benign recurrent pulmonary nodules. The authors of this study sought to identify any computed tomography (CT) imaging pattern of recurrent pulmonary metastases in this patient population. The authors also sought to identify associated prognostic factors. METHODS: CT scans obtained after thoracotomy were available for 35 patients with osteosarcoma who had undergone resection of presumed pulmonary metastases at St. Jude Children's Research Hospital (Memphis, TN). CT scans obtained before the initial thoracotomy were available for 33 of the 35. The authors recorded location, histologic diagnosis, and time of development of the original pulmonary nodules, time of recurrence of pulmonary disease; the location of recurrent nodules, and the presence of calcification, adenopathy, or progressive pleural disease, as well as patient demographic data, survival data, and location of the primary tumor site. RESULTS: Pulmonary nodules recurred in 32 of the 35 patients after thoracotomy. Nineteen of these patients underwent resection of the recurrent lesions and 1 who died underwent an autopsy; 18 of the 20 patients had metastatic disease. The only CT finding consistently associated with recurrent metastatic disease was progressive pleural thickening, which predicted a poor outcome. The occurrence of a solitary pulmonary nodule in the lung contralateral to the previous surgery was associated almost always with a benign process. CONCLUSIONS: CT imaging cannot distinguish reliably between benign and metastatic recurrent pulmonary disease after thoracotomy in patients with osteosarcoma. Recurrent pulmonary disease in this set of patients is likely to be metastatic, and aggressive surgical intervention is probably warranted. In this study, patients who had progressive pleural disease after thoracotomy consistently experienced pulmonary metastatic recurrence and had a poor prognosis.

Adolescent↗

Expression of adhesion proteins E-cadherin, alpha-catenin, beta-catenin and gamma-catenin is different in T1 and T2 breast tumours.

BACKGROUND: Breast cancer is the most common malignancy in women. Although an increasing number of patients with breast cancer are being cured by surgery, a considerable number of patients suffer relapse in the form of metastases after surgery. E-cadherin and catenins have documented roles in breast cancer progression. Mammography is supposed to decrease breast cancer mortality by detecting tumours while they are small and before they have reached a clinically detectable stage. AIM: In the present study, we wanted to evaluate whether there are differences in expression patterns of adhesion proteins, shown to be crucial in the metastatic process, between small tumours detected by mammography and clinically detected large tumours. METHODS: Expression of E-cadherin, alpha-catenin, beta-catenin and gamma-catenin was analysed using immunohistochemistry methods in 86 invasive breast carcinomas detected by mammography and compared with 90 clinically palpable invasive breast carcinomas. RESULTS: In the group of tumours detected by mammography (86 samples), reduced expression of E-cadherin was observed in 12 (14%) samples. Reduced expression of alpha-catenin was observed in four (4.6%) samples, and three (3.5%) samples showed reduced expression of beta-catenin. All samples showed strong expression of gamma-catenin. When expression patterns of these proteins were evaluated in 90 clinically detected tumours, we observed reduced expression of E-cadherin in 58 (64.4%) samples, 12 (13.3%) samples showed reduced expression of alpha-catenin, while nine (10%) samples showed reduced expression of beta-catenin. Strong expression of gamma-catenin was detected in all tumours also in this group.Statistical analyses revealed a highly significant difference in expression of E-cadherin (p<0.001). However, no statistically significant differences were observed in expression of alpha-catenin (p = 0.081) and beta-catenin (p = 0.092) between the two groups of tumours. CONCLUSION: Results indicate that T1 breast tumours harbour less alterations in E-cadherin-catenin complexes and therefore are probably less likely to disseminate, and patients probably have a better prognosis than if tumours are diagnosed as T2.

Aged↗

Metastatic choriocarcinoma presenting as a bleeding duodenal ulcer.

We report a case of a young man with a rare disease, a choriocarcinoma of the gastrointestinal tract presenting as a common entity, a bleeding duodenal ulcer. Pathological findings and strongly positive immunostains of tissue specimens for beta human chorionic gonadotrophin confirmed the entire tumor to be a choriocarcinoma ruling out the possibility of an adenocarcinoma with focal components of choriocarcinoma or a beta human chorionic gonadotrophin producing adenocarcinoma. The pattern of tumor invasion in this case is more suggestive of metastatic than primary involvement of the gastrointestinal tract. The diagnosis of primary gastrointestinal choriocarcinoma is difficult because of the need to meticulously rule out the occurrence of a primary in other organs, which at times regresses spontaneously, a diagnosis made more difficult in this case in which no autopsy was performed.

Choriocarcinoma↗

Increase in suprabasilar integrin adhesion molecule expression in human epidermal neoplasms accompanies increased proliferation occurring with immortalization and tumor progression.

In a previous prospective study of 80 patients with squamous cell carcinoma of the upper aerodigestive tract, a progressive increase in expression of the integrin cell adhesion molecule alpha 6 beta 4 in suprabasilar cell layers of the tumor parenchyma was associated with an increase in early recurrence after therapy. In this study, we determined the relationship of the altered expression pattern of the integrin to changes occurring during benign, invasive, or metastatic stages of tumor development. Suprabasilar expression of integrin alpha 6 beta 4 appeared with neoplastic transformation in benign squamous papillomas, but homogeneous expression occurred more frequently in the parenchyma of primary and metastatic squamous cell carcinomas. The variation in the extent of suprabasilar integrin expression among the tumors corresponded to the variation in the population undergoing proliferation as determined by two independent markers of proliferation. Integrin expression was quantified in primary, HPV 16 DNA-immortalized, and v-ki-ras oncogene-transformed keratinocytes, and the pattern of expression was compared with cell cycle progression. Primary keratinocyte lines showed a bimodal distribution of integrin expression, with one population showing decreased integrin expression, cell size, and a block of cell cycle progression consistent with differentiation, whereas another population exhibited high integrin expression and full progression through the cell cycle, consistent with proliferation. HPV-immortalized and v-ki-ras-transformed cell lines undergoing continuous proliferation exhibited uniformly strong integrin expression, which was similar in intensity to that observed in the proliferating population of normal keratinocytes. Similar increases in expression of two additional integrins, alpha 2 beta 1 and alpha 3 beta 1, occurred along with integrin alpha 6 beta 4 in tissue specimens and cell lines derived from neoplasms. Thus, epidermal neoplasms display an increase in a population of cells exhibiting constitutive expression of a repertoire of integrins, which is similar to that found transiently in the acute phase of epidermal wound healing, a physiological response in which hyperproliferation, retention of multiple layers of proliferating cells, and migration occur. The association of a progressive increase in suprabasilar expression of these integrins with early tumor recurrence and advanced neoplasia suggests that constitutive expression and function of the same repertoire of integrins may be advantageous, rather than sufficient, for tumor progression.

Antigens, Surface↗

Cytochemical changes in lactate dehydrogenase isoenzymes in human brain tumours.

The lactate dehydrogenase (LDH) isoenzyme patterns in benign and malignant brain tumours were determined by means of electrophoresis of the cell extracts and selective cytochemical stain of the smears. The LDH isoenzyme distribution of the cell extracts showed a pronounced cathodal shift in the malignant gliomas and metastatic carcinomas. Normal brain tissues and histologically benign gliomas, however, showed an anodal pattern with a dominance of the H-type LDH. Schwannomas and meningiomas had a midzone isoenzyme pattern with a dominant LDH3 fraction. Pituitary adenomas usually showed the LDH pattern similar to that of the normal cerebrum. The LDH M fraction could be cytochemically verified using an inhibitory effect by 2.6 M urea in staining. Astrocytomas grades 3-4 and metastatic carcinomas were characterized by loss or marked reduction of stainability by urea treatment, while astrocytomas grades 1-2 and oligodendrogliomas were resistant to urea inhibition.

Adenoma↗

Xeroderma pigmentosum variant: DNA ploidy analysis of various skin tumors and normal-appearing skin in a patient.

BACKGROUND: The patient with xeroderma pigmentosum provides an appropriate human model for the evaluation of tumor development and progression. METHODS: We describe a patient with variant-type xeroderma pigmentosum who developed actinic keratoses, a squamous cell carcinoma, and its metastasis into a lymph node. DNA ploidy was measured and analyzed in cells of these tumors and the patient's sun-exposed as well as sun-shielded skin. RESULTS: The sun-shielded skin showed a normal diploid DNA distribution pattern, while the sun-exposed skin had an increased number of hyperdiploid cells. The actinic keratosis showed further increased hyperdiploid cells. The squamous cell carcinoma showed a large number of hyperdiploid cells and formed an aneuploid cell fraction. Histographically, the aneuploid cell fraction became more apparent and was revealed to be a major fraction in the metastatic squamous cell carcinoma. CONCLUSIONS: The changes in the DNA ploidy pattern well reflect the clinical and histologic characteristics of the respective skin conditions and likely provide the cellular basis for the sequential or stepwise carcinogenic process in the patient's xeroderma pigmentosum skin. Further studies are necessary to determine whether the present results explain the similar carcinogenic process in sun-damaged skin of the nonpredisposed general population.

Aneuploidy↗

Metastatic basal cell carcinoma: four case reports, review of literature, and immunohistochemical evaluation.

CONTEXT: Metastatic basal cell carcinoma (BCC) is relatively rare and is seldom considered a complication in the routine treatment and follow-up of patients with BCC. Although multiple studies have tried to distinguish aggressive from nonaggressive BCCs, to our knowledge, no consistent clinical, histopathologic, or immunohistochemical features have yet been reported. OBJECTIVE: To report 4 cases of metastatic BCCs and to evaluate these in addition to known nonmetastatic BCCs with specific immunostains in an attempt to find distinct morphologic or immunohistochemical patterns that could be helpful in identifying aggressive BCCs. DESIGN: We reviewed 4 cases of metastatic BCCs and recorded the clinical and morphologic findings. We then searched our archives for 14 cases of BCC that followed the usual nonaggressive course. We evaluated these 18 cases with immunohistochemical stains for Ki-67, p53, and bcl-2. RESULTS: In metastasizing BCC, Ki-67 staining was slightly higher in metastatic sites than in primary sites (average 63% and 51%, respectively). p53 was expressed in 3 of 4 primary sites and 2 of 4 metastatic sites. Bcl-2 was positive in both primary and metastatic sites in 3 of 4 cases. In the 14 cases of nonaggressive BCC, staining for Ki-67 averaged 38%, p53 was positive in 11 cases, and Bcl-2 staining was noted in 13 cases. CONCLUSIONS: Overall, in the small sample that we evaluated, the immunohistochemical markers for Ki-67, p53, and Bcl-2 did not distinguish between metastatic and nonaggressive BCCs.

Adult↗

Prostate cancer and radiation therapy--the message conveyed by serum prostate-specific antigen.

PURPOSE: Prostate-specific antigen (PSA) is a powerful pretreatment prognosticator and a sensitive post-treatment outcome measure for clinically localized prostate cancer treated with radiation therapy. Today, the pretreatment serum PSA level appears to supersede both grade and T-stage as a determinant of outcome. This study was undertaken to attempt a reconciliation between the old (pre-PSA) and the new (PSA) data-in particular to address the question of why stage and grade apparently play so little role in this PSA era. METHODS AND MATERIALS: We analyzed the outcome of two cohorts of men with T1-T4, NO, or NX, MO prostate cancer, one group (648 patients) treated and followed in the pre-PSA era (1966-1988), another group (707 patients) treated and followed in the PSA era (1987-1993)--who received definitive radiation as their only initial treatment. The patterns of relapse and prognostic factors for these groups were compared and contrasted using univariate and multivariate techniques. RESULTS: At a median follow-up of 6.5 years, the relapse patterns in the pre-PSA series were: local in 109 (17%), nodal in 17 (3%), and distant metastatic in 186 (29%). Actuarial local and metastatic rates at 5 years were 13 and 26%, respectively. Local recurrence was only weakly predictable, Gleason grade being the only significant, albeit weak, covariate. Metastatic failure, however, was highly significantly and meaningfully correlated with Gleason grade and T-stage. Because metastasis was the most common adverse end point in this series, overall freedom from progression also correlated with grade and stage. At a median follow-up of 31 months, the patterns of failure in the PSA series were: local in 77 (11%), nodal in 3 (< 1%), and distant metastatic in 24 (3%). Actuarial local and metastatic rates at 5 years were 30 and 6%, respectively. Local recurrence was highly and meaningfully correlated with pretreatment PSA level, which was the only significant determinant of this end point. Metastatic failure was highly correlated with Gleason grade and T-stage, with PSA playing a much lesser, though significant role. The inversion of failure patterns (local vs. distant) between the two series was striking. The high incidence of local failure in the PSA series was almost entirely related to positive prostatic biopsies pursuant to the investigation of the postradiation rising PSA profile. Of the 77 local recurrences, 69 (90%) were identified in this way. Among 99 men with rising PSA values who underwent investigation (CT scans, bone scans, and biopsies), disease was found in 86, and the patterns of disease in these 86 were: local only in 62 (72%), local and metastatic in 7, and metastatic in 17 (20%). The most common event in the PSA series was the rising PSA profile, and this, too, strongly correlated with the pretreatment PSA level. CONCLUSION: Based on our earlier finding that the major source of pretreatment serum PSA in patients with clinically localized disease is the primary tumour itself and on the findings in the present report, we conclude that the new major message conveyed by serum PSA relates to the primary tumor and its likely outcome. Gleason grade and T-stage remain major determinants of metastatic relapse. The total and permanent eradication of prostate cancer from the prostate with conventional doses of external beam radiation therapy is harder to achieve than generally appreciated.

Adenocarcinoma↗

Subcellular localization of HMFG2 in breast carcinomas: an immunohistochemical and immunoelectron microscopic study.

Malignant transformation of human cells is associated with morphological and biochemical alterations. We have studied the distribution and pattern of staining of HMFG2 (human milk fat globulin) in normal breast, benign breast lesions, and 137 primary and metastatic breast carcinomas. Immunohistochemical staining was performed with an antibody to HMFG2 using the indirect peroxidase technique. Three patterns of staining were noted: 1) secretion and luminal staining (in normal breast, most benign breast lesions and some breast carcinomas); 2) plasma membrane staining (in breast carcinomas); 3) intracytoplasmic staining (in breast carcinomas). Immunoelectron microscopy was also performed on normal breast, infiltrating duct, and lobular carcinomas. Immunoelectron microscopy showed localization of the gold particles on the electron dense granules of the HMFG2 protein. These were localized along the surface of the extracytoplasmic lumina in normal breast ducts/acini and breast carcinomas, whereas localization was also noted within the intracytoplasmic lumina in cancer cells only. These results show that there is altered localization of milk fat globulin in breast cancer cells associated with membrane internalization and formation of intracytoplasmic lumina. This contributes to the understanding of the phenotypic alterations associated with malignant transformation in breast cancer.

Breast Diseases↗

The course of metastatic disease originating from carcinoma of the prostate.

The purpose of this work was to study the time sequence and the patterns of the multistep spread of metastases. Fifty-one patients with stage D carcinoma of the prostate, previously treated for their primary tumor by surgery or radiotherapy combined with hormonal manipulation and for metastases by hormones and chemotherapy, were included in the study. The metastatic dissemination, characterized primarily by the appearance of bone metastases, could follow two distinct patterns: The first, characterized by sequential appearance of osteoblastic metastases, followed by the development of osteolytic bone lesions, and the second pattern, characterized by the simultaneous appearance of osteoblastic and osteolytic bone lesions. In cases with solely osteoblastic bone metastases, the lesions are hormone sensitive and long-lasting remissions could be obtained. The development of osteolytic bone lesions is usually accompanied by the recurrence of the primary tumor and appearance of metastases in other sites, such as the lymph nodes and lungs. Bone metastases became resistant to hormonal manipulation and with chemotherapy short remissions were obtained. The course of the terminal period is faster, with shorter survival times. The determination of serum acid and alkaline phosphatase levels seems to reflect the course of the disease during the initial period of the disease only, i.e. when bone metastases are sensitive to hormonal treatment.

Acid Phosphatase↗

Lace-like enhancement pattern of osteosarcoma of rib and liver metastasis in CT scans.

The rib is an uncommon site of osteosarcoma. With the use of adjuvant chemotherapy and aggressive surgical resection of the metastatic pulmonary lesions, extrapulmonary metastases are becoming more clinically evident. Primary rib osteosarcoma with extrapulmonary metastasis is exceedingly rare. A case is reported, showing that the pattern of metastasis of rib osteosarcoma is similar to that of primary bone osteosarcoma. The liver metastasis occurred after resection of the metastatic pulmonary lesions. A CT scan of the primary rib lesion and liver metastasis both showed a lace-like enhancement pattern, its histological appearance corresponding with neoplastic osteoid. With the increasing use of CT abdomen for localization of extrapulmonary metastases, lace-like enhancement may be seen more readily in the future.

Adult↗