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PubMed1989

Application of immunohistologic staining to develop a malignant index to aid in distinguishing benign from malignant prostatic tissue.

The development of antisera with reactivities against intermediate filaments, differentiation antigens, and secretory products has aided in identification and characterization of tissue specimens. Such evaluations may assist pathologists in distinguishing between benign (BPH) and malignant (CAP) tissue of prostatic origin. However, attempts to employ this technique are thwarted by 1) the use of frequently incompletely characterized antisera, 2) the use of both paraffin- and frozen-sectioned materials, and 3) a lack of quantitation in the degree of antisera immunoreactivity. To overcome these shortcomings, a mathematical approach was evaluated using eight BPH and 23 CAP specimens. These were sectioned and stained using commercially prepared antisera against cytokeratin (Cyto P, Cyto M), epithelial membrane antigen (EMA), NK cells (Leu-7), prostatic acid phosphatase (PAP), and prostate specific antigen (PSA). Reactivity was quantitated on a scale of 0-5. Mean values for markers elevated in CAP (relative to BPH) were placed in the numerator; those elevated in BPH (relative to CAP) were placed in the denominator: Malignant index = PSA + EMA + Leu-7 + Cyto M/PAP + Cyto P. This malignant index was significantly greater (P less than .001) in CAP tissues than in BPH regardless of Gleason grade (3.2 +/- 0.9 vs 1.6 +/- 0.9). It was also significantly elevated (3.0 +/- 0.8; P less than .01) in nine specimens representing prostatic atypical hyperplasia. These data suggest that immunohistologic staining may be applied as an aid in distinguishing between BPH and CAP.

Diagnosis, Differential↗

PubMed1996

Differential reactivity of HBME-1 and CD15 antibodies in benign and malignant thyroid tumours. Preferential reactivity with malignant tumours.

We studied a wide range thyroid tumours and non-neoplastic conditions (total 463 cases) immunohistochemically to evaluate the possible diagnostic potential of HBME-1 and CD15 antibodies. HBME-1 monoclonal antibody recognizes a biochemically unknown epitope present in mesothelioma and variably present in some adenocarcinomas. CD15 antibodies recognize a sugar epitope also included in Lewis X blood group antigen. All papillary (145/145) and follicular carcinomas (27/27) were HBME-1 positive, usually in the the majority of tumour cells. In contrast, cases of nodular goitre and papillary hyperplasia either showed no reactivity or were focally positive (in a third of cases). The patterns of CD15 reactivity were generally similar, although smaller numbers of tumour cells were positive in papillary carcinomas, and only 50% of follicular carcinomas were positive. Because fetal thyroid also showed CD15 reactivity, this antigen appears to behave as an oncofetal antigen in relation to thyroid tissue. Anaplastic carcinomas were negative with both antibodies, indicating the loss of these epitopes upon high grade malignant transformation. We conclude that HBME-1 and CD15 immunohistochemistry may be helpful in the histological differential diagnosis between benign lesions and differentiated thyroid carcinomas, especially papillary tumours. Although the biochemical basis of HBME-1 reactivity is unknown, increased CD15 reactivity in malignant thyroid tumours probably reflects changes in thyroid follicular epithelial glycoconjugates related to malignant transformation.

Adenocarcinoma, Follicular↗

PubMed1983

Proliferating cell nuclear antigen (PCNA) and human malignant tumor nucleolar antigens (HMTNA) in nucleoli of human hematological malignancies.

Lymphoma (Lymphocytic non-Hodgkin's malignant lymphoma) and leukemic (chronic lymphocytic, acute and chronic myeloid, myelomonocytic leukemia) cells were studied by indirect immunofluorescence to evaluate the presence of proliferating cell nuclear antigen (PCNA) and human malignant tumor nuclear antigen (HMTNA) in their nucleoli. Most cells in lymph node smears of lymphocytic non-Hodgkin's malignant lymphoma (NHML) developed a bright nucleolar fluorescence with HMTNA antibodies. PCNA was detected in nucleoli of a limited number of cells which apparently represent the proliferating cell population in these lymphomas. Similarly, in the bone marrow smears of patients with chronic lymphocytic leukemia most cells possessed a nucleolar fluorescence for HMTNA and PCNA was present in nucleoli of a limited number of cells. In the bone marrow smears of patients with myeloid or myelomonocytic leukemias most blastic or monocytoid cells also developed a bright nucleolar fluorescence with HMTNA antibodies and PCNA was present only in a small percentage of these cells. Leukemic cells with PCNA in their nucleoli like thekhuntigen might represent a proliferating cell population in late G1-early S phase.

Antigens, Neoplasm↗

PubMedDate not supplied

How malignant is malignant? A brief review of the microscopic assessment of human neoplasms, and the prediction of whether they will metastasize and kill.

This review examines ways in which histopathologists can attempt to predict the degree of malignancy from the microscopic examination of surgically removed samples of human neoplasms. These include mitotic counts, measurement of DNA content, analysis of DNA turnover, measurement of proliferation antigens, measurement of nucleolar organizing areas, counting nucleoli, morphometry of nuclei, identification of genetic change, measurement of lysis of basement membrane, and measurement of invasion in vitro. The latter two are not currently of practical value. Of the rest none is uniformly capable of predicting the degree of malignancy of a human neoplasm. After further refinement and control measurement of several such parameters may however contribute more to the prediction of malignancy than present subjective assessments.

Basement Membrane↗

PubMed2002

A rare association between malignant mediastinal seminoma and other malignant neoplasms.

Primary malignant mediastinal seminomas (PMMS) are rare tumors accounting for 1-6% of all mediastinal tumors. PMMS mostly affect young men, arising from primordial germ cells that abnormally migrate from the ectoderm of the yolk sac to the gonadal region. They are clinically and biologically distinct from primary testicular tumors and seem to have a worse prognosis. Due to the rarity of the disease, the choice of treatment is a matter of debate. Literature data do not show any association between this kind of tumor and malignant Schwannoma or thyroid carcinoma. In this report we describe the case of a patient affected by PMMS and 12 yr later by a malignant brachial plexus Schwannoma and papillary thyroid carcinoma (PTC). Since both mediastinal seminoma and Schwannoma were treated with surgery followed by local radiotherapy, we were not able to ascertain if either PTC or Schwannoma had been induced by radiotherapy or represented a casual neoplastic association.

Brachial Plexus Neuropathies↗

PubMed2006

[Secondary malignancies after successful primary treatment of malignant Hodgkin's lymphoma].

Malignant Hodgkin's lymphoma (HL) has become a curable disease through the increasing intensity of the treatment strategies applied. These regimens are aggressive, including radiotherapy and chemotherapy leading to the possibility of secondary malignancies. The German Hodgkin Lymphoma Study Group considered three cohorts including 5,411 patients with all stages of HL. In 127 patients a secondary solid tumor was diagnosed (cumulative risk 2%, median follow-up 72 months), with bronchial carcinomas (23.6%) and colorectal adenocarcinomas (20.5%) being the most frequent neoplasms. Secondary acute myeloid leukemia was found in 36 patients, another ten developed myeloid dysplasia (cumulative risk 1%, median follow-up 55 months). A total of 52 patients revealed a non-Hodgkin's lymphoma (NHL; cumulative risk 0.9%, median follow-up 46 months). The overall incidence of secondary malignancies was 3.9% in patients who had been treated successfully for their HL with radio- and/or chemotherapy.A secondary NHL can be particularly difficult to be distinguished from the preceding HL. Therefore, in case of a suspected relapse, a complete histopathological work-up must be performed.

Antineoplastic Agents↗

PubMed2005

Malignant meningioma as a second malignancy after therapy for acute lymphatic leukemia without cranial radiation.

RATIONALE: Meningiomas in the pediatric age group are very rare tumors, comprising about 1-4.2% of all primary pediatric intracranial tumors. CASE REPORT: We present a 17-year-old patient who suffered from an intraventricular malignant meningioma. At the age of 2 years, acute lymphatic leukemia (common ALL [cALL]) was diagnosed and successfully treated with chemotherapy. There was no cranial radiation therapy. In December 2001, 13 years after diagnosis of cALL, he complained of headache, vomiting, and walking difficulties. Magnetic resonance imaging showed an enhancing mass with cystic components in the trigone of the right lateral ventricle. The tumor was removed completely. Histological diagnosis revealed a malignant papillary meningioma. After removal of a recurrent meningioma 16 months later, he received local radiotherapy. CONCLUSION: Pathogenetic mechanisms, treatment options, and prognosis of meningiomas and secondary malignancies of this age group are discussed.

Adolescent↗

PubMed2001

Spitzoid malignant melanoma with lymph-node metastasis. Is a copy-number loss on chromosome 6q a marker of malignancy?

Distinction of spitzoid malignant melanomas (SMM) from Spitz nevi may be difficult or even impossible on the basis of conventional histology. In this report, a patient suffering from a primary lesion diagnosed as a Spitz nevus and a metastatic malignant melanoma approximately 4 years thereafter is described. A diagnosis of SMM was made subsequently upon review of the primary lesion. In the present analysis, we used comparative genomic hybridization (CGH) to define markers characteristic of SMM. The primary lesion revealed deletions on chromosomes 6q and 9p. In the metastasis, additional deletions on chromosomes 10p and 10q and gains of chromosome 7 were found. To our knowledge, no chromosomal aberration on chromosome 6 was hitherto demonstrated in benign melanocytic nevi. Findings reported in the literature suggest that human melanoma metastasis suppressor gene maps to 6q. In contrast, losses on chromosome 9p seem to be an early event in the development of melanoma. However, they are not only found in melanomas but are occasionally present in Spitz nevi as well as in atypical nevi. The CGH result with deletion of 6q in this difficult to diagnose primary melanocytic lesion strongly supports the diagnosis of malignant melanoma. To demonstrate the reliability of loss on chromosome 6q as a marker of SMM, a larger number of lesions must be investigated.

Adolescent↗

PubMed2002

[Degos atrophic malignant papulosis. Not always malignant!].

A patient developed malignant atrophic papulosis with only cutaneous manifestation. Repeated coloscopy uncovered no malignant papules in the colon. Referring to the literature, the value of permanent anticoagulant therapy is discussed. In contrast to the term "malignant" atrophic papulosis, there also seems to be a variant with a benign clinical course.

Adult↗

PubMed1989

Thrombospondin in malignant and non-malignant breast tissue.

Cytosols of malignant breast tissue contained significantly higher levels of thrombospondin (TSP) and von Willebrand factor (vWF) than non-malignant breast. TSP and vWF content of human breast were significantly correlated whereas there was no correlation between TSP and the platelet-specific protein beta-thromboglobulin (beta TG). Whilst TSP in pre-menopausal breast cancer was slightly lower than in post-menopausal breast cancer, it did not correlate with oestrogen receptors (ER) or progesterone receptors (PR), but was negatively correlated with tissue-type plasminogen activator (tPA), an oestradiol-inducible enzyme. Secretion of TSP by MCF-7 cells was low and refractory to hormones. High levels of TSP appeared to be associated with the centre of the tumour mass. It is suggested that activation of the endothelium may be responsible, at least in part, for the high levels of TSP found in malignant breast tissue and could be a factor in the growth and spread of breast cancer.

Breast↗

PubMed1993

Expression of cathepsin D in malignant and in the corresponding non-malignant node-negative laryngeal samples: correlation with receptors for androgen, glucocorticoid, oestrogen and progesterone.

A standard immunoradiometric technique was used to investigate the distribution of the intracellular aspartic proteinase cathepsin D in 33 malignant and in the corresponding histologically-proven non-malignant fragments obtained from lymph node negative patients suffering from larynx cancer. In both tissues the androgen, glucocorticoid, oestrogen and progesterone receptors were also assayed. Our data indicate that cathepsin D was present in both tissues, with level significantly higher (P < 0.0001) in the cancerous fragments (with a mean of 33 +/- 3.4 pmol/mg protein) than in the corresponding non-cancerous specimen (with a mean of 20.8 +/- 2 pmol/mg protein). A significant positive association (P < 0.001) between cathepsin D and PR concentration values in the cancerous larynx was observed; accordingly, tumours expressing PR had significantly (P = 0.0005) higher cathepsin D levels than the tumours which did not contain the receptor. In contrast, such a relationship was absent in the non-malignant specimens. As regards the other steroid receptors, no significant relationship between them and cathepsin D was observed. We conclude that cathepsin D may have a role also in laryngeal carcinoma and that its association with the PR could indicate a possible role of the receptor in the biology of this disease.

Aged↗

PubMed1993

Human herpes simplex-1 and papillomavirus type 16 homologous DNA sequences in normal, potentially malignant and malignant oral mucosa.

We have tested a range of normal, potentially malignant and malignant oral mucosal biopsies tissues by Southern blot hybridisation analysis for the simultaneous presence of HSV-1 and HPV type 16 DNA sequences, both of which have been implicated as risk factors in oral carcinogenesis. The results show that: (1) 2/4 patients with lichen planus, 2/4 patients with non-specific keratosis, 1/8 patients with oral carcinoma and 3/5 biopsy specimens of normal oral mucosa contained DNA sequences homologous to the HSV-1, Bam HI-G fragment. (2) HPV-16 homologous DNA sequences were detected in 3/4 patients with lichen planus, 4/4 non-specific keratosis, 4/8 oral carcinomas and in 3/5 biopsy specimens of normal oral mucosa. (3) Overall, only 5 patient biopsy specimens were positive for both HSV-1 and HPV-16 homologous DNA sequences; 2 lichen planus, 2 non-specific keratosis and 1 normal. The data cannot exclude a "hit and run" oncogenic mechanism for HSV but suggest that if HSV-1 and HPV-16 play a synergistic role in the development of oral cancer this may be an early event. Indeed, the data suggest HSV might be more frequently found in potentially malignant lesions than in carcinoma.

Adolescent↗

PubMed2005

Involvement of oxidative stress in the pre-malignant and malignant states of cervical cancer in women.

OBJECTIVES: To evaluate the potential role of oxidative stress in the evolution of cervical cancer, including its pre-malignant states. DESIGN AND METHODS: Erythrocytes thiobarbituric acid reactive substances (TBARS) levels, plasma vitamin C and thiol content and total blood delta-ALA-D levels were estimated in 46 untreated cervical cancer and pre-malignant patients and in 46 age-sex-matched controls. RESULTS: Erythrocytes from patients, regardless of disease state, pre-malignant (low squamous intraepithelial lesion--LSIL and high squamous intraepithelial lesion--HSIL) or cancer, showed a significant 2-3 times increase in TBARS levels (P<0.01). Plasma vitamin C was lower in the carcinoma group (P<0.01). The reactivation index of delta-aminolevulinate dehydratase (delta-ALA-D) was higher in the patient group, when compared to control (P<0.01). CONCLUSION: LSIL, HSIL or cervical cancer can be associated with changes in 3 indicators of oxidative stress: increase in erythrocyte TBARS, ALA-D reactivation index and a decrease in vitamin C content, that may play an important role in carcinogenesis.

Adult↗

PubMed1986

Malignant gonadal stromal tumor of the testis arising with a malignant teratoma.

We report a case of a rare malignant gonadal stromal tumor arising with a malignant teratoma of the testis. The malignant gonadal stromal element of the tumor or the nongerminal cell component was resistant to chemotherapy and ultimately metastasized to the lymph nodes, lung, bones and liver. Nongerminal cell tumors arising with germinal cell neoplasms may become more common because the chemosensitive germ cell tumor may be destroyed and the chemoresistant nongerminal tumor remains. The nongerminal cell tumor is the most important prognostic factor and also dictates possible later changes in therapy.

Adult↗

PubMed1977

Ovarian epithelial tumors of borderline malignancy (carcinomas of low malignant potential).

Ovarian epithelial neoplasms that have morphologic features intermediate between those of clearly benign and unquestionably malignant lesions are currently classified as tumors of borderline malignancy (carcinomas of low malignant potential). Patients with stage I lesions of this type have an excellent prognosis following conservative surgery. Survival rates are remarkably good even when extraovarian spread has developed. The clinicopathologic features and histologic criteria for the diagnosis of borderline tumors of serous and mucinous cell types are detailed in this presentation.

Cystadenoma↗

PubMed1979

Malignant soft tissue tumors (malignant fibrous histiocytoma, pleomorphic liposarcoma, and pleomorphic rhabdomyosarcoma): an electron microscopic study.

A comparative ultrastructural analysis of malignant soft tissue tumors (malignant fibrous histiocytoma, pleomorphic liposarcoma, and pleomorphic rhabdomyosarcoma) revealed similar ultrastructural features in this group of tumors. However, by electron microscopy these tumors can be differentiated on the basis of cytoplasmic and extracytoplasmic features (myosin filaments, lipid droplets, and perinuclear intermediate filaments, for example). This is even true of less well differentiated tumors and tumor cells. These findings support and amplify the concept of a common histogenesis for tumors of mesenchymal origin. Paradoxical features observed by light microscopy warrant further study by electron microscopy if the correct diagnosis is to be made in atypical cases, such as apparent malignant fibrous histiocytoma with cross striations.

Adult↗

PubMed1998

Dipeptidyl peptidase III in malignant and non-malignant gynaecological tissue.

Exopeptidases, in contrast to endopeptidases (proteinases) have been much less studied in relation to cancer. The aim of this study was to investigate one such enzyme, dipeptidyl peptidase III (DPP III), in gynaecological tissues, by measuring both the enzyme activity and enzyme content. DPP III activity was assessed in normal (n = 65), benign (n = 9) and malignant (n = 51) gynaecological tissues. A statistically significant higher DPP III activity was observed in endometrial (n = 40, P = 4.6 x 10(-7)) and ovarian (n = 11, P = 8.1 x 10(-4)) malignant tumours, whereas no significant difference was detected for leiomyomas (n = 8), if compared to the activity in normal tissue. A matched pair analysis of normal and cancerous endometrial tissue confirmed the significance of the DPP III activity increase in the transformed tissue (n = 7, P = 0.022). Western blot analysis revealed a significantly (P = 0.014) increased level of DPP III in endometrial cancer. Further, regression analysis showed a positive correlation between the activity and the content of DPP III in normal tissue (r = 0.637, P = 0.047) and in endometrial cancer (r = 0.574, P < 0.007). The increase of the DPP III activity was observed in the endometrial carcinomas of various histological types, grade or the depth of myometrial invasion. The easy-to-perform determination of this exopeptidase activity may serve as a potential indicator of endometrial and ovarian malignancies.

Adolescent↗

PubMed2003

Scavenger receptor class B, type I on non-malignant and malignant human epithelial cells mediates cholesteryl ester-uptake from high density lipoproteins.

Hepatoma cell lines serve as a suitable model to study hepatic clearance of lipoprotein-associated cholesteryl esters (CEs). The present study aimed at investigating holoparticle-association of and selective CE-uptake from human high density lipoprotein subclass 3 (HDL3) by non-malignant adult (Chang-liver) and non-malignant fetal (WRL-68) epithelial cell lines as well as a hepatocellular carcinoma (HUH-7) cell line. Binding properties of 125I-HDL3 at 4 and 37 degrees C were similar for all three cell lines while degradation rates were highest for Chang-liver cells. Calculating the selective uptake of HDL3-associated CEs as the difference between [3H]CE- and 125I-HDL3 cell-association revealed that the selective lipid uptake and holoparticle-association was similar in Chang-liver while in WRL-68 and HUH-7 cells pronounced capacity for lipid tracer uptake in excess of holoparticle uptake was measured. Using RT-PCR, Northern and Western blot analysis, as well as immunocytochemical technique pronounced expression of scavenger receptor class B, type I (SR-BI) but not SR-BII (a splice variant of SR-BI less efficient for selective CE-uptake than SR-BI) could be identified in HUH-7 and WRL-68 cells. A polyclonal antiserum raised against SR-BI significantly decreased cell-association of [3H]CE-HDL3 in HUH-7 and WRL-68. The present findings suggest that the capacity for selective cholesteryl ester-uptake from high density lipoprotein by malignant and normal epithelial cells from the liver depends on expression of the scavenger receptor class B, type I.

Animals↗