Biomedical subjects
J Hassoun
Publications and source records attributed to J Hassoun.
[Tumors of the breast. Pathological anatomy].
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Unrestricted T-cell receptor V-region gene repertoire in tumor-infiltrating lymphocytes from human breast carcinomas.
BACKGROUND: Several lines of evidence indicate that a more favorable prognosis is correlated with the degree of lymphocyte infiltration within breast carcinomas. The characterization of these T-cell infiltrates appears necessary to explore the possible existence of an in situ immunologic response of the host against neoplastic cells. Previous studies have indeed suggested that the T-cell receptor (TCR) repertoire of tumor-infiltrating T-lymphocytes (TIL) should be restricted if they act specifically against tumor-related antigens. METHODS: To address this question, the expression of variable (V) region genes of the TCR-alpha and beta chains in intratumoral lymphocytes from five breast carcinoma biopsy specimens and one normal mammary gland specimen was analyzed using the polymerase chain reaction (PCR). The neoplastic samples included one medullary carcinoma and four ductal infiltrating carcinomas selected on the basis of a rich lymphoid stromal component. Primers specific for 18 different V alpha and 21 V beta families were used for PCR. RESULTS: In every case, TIL showed an unrestricted pattern of TCR V-region gene expression, similar to the repertoire observed in peripheral blood lymphocytes and in the normal breast tissue. CONCLUSIONS: According to these nonquantitative PCR experiments, the apparent lack of selection of a limited number of T-cell specificities in the affected tissues does not favor the existence of an in vivo lymphoid recruitment based on TCR recognition of neoplastic antigenic determinants. Further studies, however, leading to an accurate quantification of immunologically relevant T-cell clones and including larger series of cases still are necessary before it will be possible to draw a final conclusion.
Tyrosinase gene expression in human tissues.
The occasional occurrence of primary extra-cutaneous malignant melanomas (MM) has led to the hypothesis that melanocytes derived from the neural crest may be arrested in their migration and may undergo an in situ malignant transformation. However, aggregates of nevus cells have only rarely been identified by histological examination in a few organs other than skin and eye. Tyrosinase is a melanin biosynthetic enzyme that is considered one of the most specific markers of melanocytic differentiation. We have attempted to detect cells committed to the melanocytic lineage, in human tissues, by means of tyrosinase gene expression. Total RNA was extracted from normal and neoplastic tissues and analyzed using a highly sensitive reverse transcription PCR assay with primers specific for the tyrosinase gene. Peripheral blood mononuclear cells (PBMC) from healthy subjects were used as negative controls. Tyrosinase transcripts were identified in a wide range of normal organs such as skin, lymph nodes, antrum, colon, kidney, lung, testis, ovary, breast, and peripheral nerve. Tyrosinase RNA was also detected in neoplastic samples including benign cutaneous nevi, lymph nodes involved by MM, breast carcinoma, liposarcoma, malignant lymphoma, and schwannoma. PBMC from patients with metastatic MM were also positive, while no positivity was detected in blood specimens from patients with other cancers. Therefore, it appears likely that cells expressing the tyrosinase gene are present in a wide range of human tissues. Although these cells still have to be accurately identified, one could propose that they might correspond to either fully differentiated melanocytes, melanocytic precursors, or Schwann cells bearing potentialities of melanocytic differentiation.(ABSTRACT TRUNCATED AT 250 WORDS)
Central neurocytoma: a synopsis of clinical and histological features.
The central neurocytoma is a supratentorial, often calcified brain tumour affecting young adults and is typically located in the lateral ventricles in the region of the foramen of Monro. Clinically, the tumour causes signs of increased intracranial pressure, visual and mental disturbances and, occasionally, pyramidal or endocrine symptoms. By light microscopy, the tumour is composed of small round cells in a delicate fibrillary matrix. Tumour cells consistently show features of neuronal differentiation by electron microscopy (synapses, dense-core vesicles, presynaptic clear vesicles, specialized synaptic junctions) and immunoreactivity for synaptophysin and other neuronal marker proteins. The tumour can be totally removed in nearly half of the cases. After incomplete surgical resection neurocytomas may recur but because of their low proliferation potential, radio- or chemotherapy are not generally recommended. Postoperative recurrence-free survival times of up to 19 years have been reported. Neurocytomas constitute nearly one half of supratentorial intraventricular tumours in adults but amount to less than 1% of all tumours of the central nervous system and its coverings.
[Gastric adenocarcinoma with an endocrine component. Report of nine cases].
Nine gastric adenocarcinomas containing endocrine cells were retrospectively studied to evaluate anatomo-clinical and immunohistochemical features, and the out-come of the patients. These gastric tumors were bulky with frequently lymph node metastasis. The immunohistochemical analysis had shown that all tumors contain EC cells, two tumors D cells, one tumor PP cells, but neither G cells nor A cells were detected. Five-years survival rate of these gastric tumors was slightly but not significantly increased as compared to usual adenocarcinomas (45.5% vs 36.5%). However, one can raise the question of possible control of local hormonal secretions on tumoral growth, particularly the anti-trophic part of the somatostatin.
In situ expression of the IL-1-alpha and TNF-alpha genes by Reed-Sternberg cells in Hodgkin's disease.
The histopathologic pattern of tissues involved by Hodgkin's disease (HD) suggests excessive activation of environmental cells by cytokines released by Hodgkin-Reed-Sternberg (HRS) cells, which are considered as the neoplastic component of HD lesions. This hypothesis has been supported by many studies performed in vitro using HD cell lines. In this study, we have tried to demonstrate the cytokine-producing cells in an environment as close as possible to the in vivo conditions, using in situ hybridization onto frozen sections of HD samples. [35S]-labelled single-stranded RNA probes were prepared by transcribing human cDNA fragments of the TNF-alpha and IL-1 alpha genes subcloned into appropriate vectors. A total of 19 specimens of HD lesions, including 7 cases of nodular sclerosing (NS) type and 12 cases of mixed cellularity (MC), were tested with both types of probes. Clinical stages included stage I (6 cases), stage II (4 cases), stage III (6 cases) and stage IV (3 cases). TNF-alpha and/or IL-1 alpha expression was observed in 12 among 19 HD cases. However, neither the histological type nor the clinical status of the patients was correlated with the profile of cytokine secretion. Most of the cytokine-producing cells could be identified as HRS cells due to their morphological appearance. In 3 cases, simultaneous analysis by immunohistochemistry and in situ hybridization showed that IL-1 alpha/TNF-alpha mRNA-producing cells simultaneously expressed the CD30 antigen, thereby confirming the HRS nature of these cells.
Central neurocytomas. Critical evaluation of a small-cell neuronal tumor.
We report herein the clinical and pathological features of 20 patients with central neurocytomas. Investigations for various differentiation antigens and cell type-specific markers were performed by immunohistochemistry using paraffin-embedded tissue. In addition, the expression of L1 adhesion molecule and of the various N.CAM (neural cell adhesion molecule) isoforms were investigated by immunoblotting studies in two frozen specimens. Central neurocytomas are clinically characterized by their intraventricular localization, occurrence in young adults, and good prognosis. It rarely occurs in patients over 50, but such cases have a poor prognosis. Total surgical excision is the best treatment. Radiotherapy is appropriate if surgery is incomplete or contraindicated. Histologically, central neurocytomas display the following features: an oligo-like pattern, usually associated with large fibrillary rosettes or perivascular arrangement, and a rich endocrine-type vasculature. Central neurocytomas have a remarkably homogeneous antigenic profile. GFAP expression is only found in scattered reactive astrocytes, S100 protein in reactive astrocytes and rare tumor cells. Among the pan-neuroendocrine markers, central neurocytomas always express neuron-specific enolase; they frequently express synaptophysin but never chromogranin A. Synaptophysin is the most reliable immunohistological marker for central neurocytomas; however, immunoreactivity could be lost with long formalin fixation. In these cases, electron microscopy is used to support the neuronal nature of the tumor cells. The expression of L1 adhesion molecule and the isoform 180 of N.CAM, indicates that central neurocytomas are formed by cells committed to neuronal phenotype. Nevertheless, advanced neuronal differentiation may be absent, as suggested by the persistence of embryonic N.CAM, the nonexpression of neurofilament proteins, and the absence of mature synapses in numerous cases. Central neurocytomas and neuroblastomas share some biochemical properties, but their respective clinicopathological features and biological behavior are dramatically different.
Detection of gastrin mRNA by in situ hybridization using radioactive- and digoxigenin-labelled probes: a comparative study.
The hormone gastrin is mainly produced by the G cells of the antral mucosa and plays a major role in the regulation of digestive mucosal growth. Since it permits identification of cell types containing mRNA, in situ hybridization (ISH) appears to be an interesting method for studying gastrin-producing tissues. In this study, in situ detection of gastrin mRNA has been carried out on frozen sections of four human normal antral mucosa samples and of six colonic carcinomas removed from patients with high levels of plasma gastrin, using a gastrin oligonucleotidic DNA probe. We have compared the results provided respectively by the [35s] labelling and the digoxigenin labelling of the synthetic probe. Positive cells were found in each normal sample analysed with radioactive- as well as digoxigenin-labelled antisense probes. The total number of cells expressing gastrin mRNA appeared slightly higher with the [35s]-labelled probe, while the digoxigenin-labelled probe gave a better definition of positive signals. In contrast, neither radioactive nor cold probes gave positive signals in the six colonic carcinoma samples, although gastrin expression had been demonstrated in these tumours using a reverse transcriptase-PCR method. These results show that, although ISH does not seem sensitive enough to allow the detection of very low levels of gastrin expression, it would appear to be a reliable method for visualizing gastrin mRNA in human antral mucosa.
Cutaneous lymphomas of phenotypically undetermined lineage: contribution of genotypic analysis.
Genotypic analyses were performed in six primary cutaneous lymphomas whose lineage could not be assessed on the basis of histologic and phenotypic data. By immunophenotyping, these neoplasms expressed leukocyte common antigen and HLA-DR but did not show consistent immunostaining for B-cell or T-cell differentiation antigens. Expression of nonspecific histiocytic markers such as lysozyme and alpha 1-antitrypsin was found in three cases. By genotyping, three cases retained a germline configuration and immunoglobulin gene rearrangement was observed in one case, T-cell receptor gene rearrangement was found in one case, and both types of rearrangements in one case. Of the three patients in whom gene rearrangements were noted, two rapidly died and the other patient, with a dual genotype, is still alive 15 years after diagnosis. The three patients without gene rearrangements are alive and well after a mean follow-up of 2.5 years. It appears that cutaneous lymphomas with an uncertain phenotype include at least some cases of authentic B-cell or T-cell lymphomas. The germline configuration that we observed in cases with a chronic course remains difficult to explain. It may be related to a low malignancy form of histiocytic lymphoma, an atypical polyclonal hyperplasia, or even a low-grade lymphoma arising from a primitive cell without established commitment to either B- or T-cell lineage.
Extra-anogenital HPV16-related bowenoid papulosis.
In this report we describe a case of bowenoid papulosis (BP) on the face of a 44 year old Algerian man. To our knowledge this is the first reported case of isolated extragenital BP. The presence of type 16 human papilloma virus was demonstrated by in situ hybridisation. This case underscores that multiple HPV-induced severe intraepithelial neoplasia, the so-called BP, is not restricted to the anogenital area.
Malignant transformation of an osteoblastoma of the skull: an exceptional occurrence. Case report.
What is apparently the first reported case of spontaneous malignant transformation of a benign osteoblastoma of the skull is described. The initial lesion was completely removed surgically and showed the histological features typical of a benign osteoblastoma. No radiotherapy was performed. Eleven years later the patient developed an osteosarcoma of the skull. Review of the literature showed that malignant transformation of benign osteoblastomas is extremely rare and could take place spontaneously. However, the risk of this occurring seems higher after inadequate initial treatment (curettage or partial excision). Follow-up monitoring of patients with osteoblastoma of the cranial vault is suggested.
Lymphadenopathic tumor exhibiting intermingled features of Kaposi's sarcoma, malignant lymphoma, and angiofollicular hyperplasia.
A 56-year-old man presented with an inguinal lymph node enlargement. Histologic study of the tumor revealed three intermingled pathologic lesions: a nodular small cell lymphoma, an angiofollicular hyperplasia of vasculohyaline type, and a vascular neoplasia closely resembling Kaposi's sarcoma. The patient was immunocompetent and denied any homosexual relationships, transfusions, or drug use. The serum was negative for the presence of human immunodeficiency virus antibody. Computed tomographic scan and ultrasound examination revealed no other lymphadenopathies. This case shows that both hyperplastic and neoplastic lymphoid proliferations can occur simultaneously with vascular neoplasia. It thereby suggests that the neoplastic populations might interact to favor the tumor growth, the sequence and the nature of the stimulating events remaining unclear.
[Genotypic analysis of malignant lymphomas].
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[Human breast cancer embedded in paraffin, fixed in Bouin's fluid. Immunohistochemical analysis of estrogen and progesterone receptors].
A new immunohistochemical method using a monoclonal estrogen receptor (ER) antibody and a progesterone receptor (PR) antibody has been performed to determine hormonal receptors on Bouin's liquid fixed and paraffin embedded tissue. This technique has been evaluated by comparison with conventional immunohistochemistry on frozen sections for 100 surgical biopsy specimens of breast carcinoma Erica (C) Prica (C); in 77 of these cases it was compared with enzyme immunoassay analyses (ER-EIA, PR-EIA). After a pretreatment by proteinase K for ER, the two specific monoclonal antibodies ER or PR were incubated overnight and revealed with a streptavidin biotin complex. The specific staining for ER and PR were exclusively located in the nuclei of cancer cells in both paraffin for ER and PR were exclusively located in the nuclei of cancer cells in both paraffin and frozen sections. The results on paraffin-embedded material were compared successively with ERICA (C) and ER-EIA and with PRICA (C) and PR-EIA. In 100 breast infiltrating carcinomas studied simultaneously on both paraffin and frozen sections, the concordance was 82% for ER and 85% for PR. In 77 breast carcinoma studied simultaneously on paraffin sections and EIA, the concordance was 74% for ER and 79.2% for PR. These results suggest that in the absence of frozen material, an immunohistochemical method on paraffin-embedded material can be used with a lower sensibility than on frozen sections. However, the detection of both ER and PR allows the identification of the hormondependent cases.
Fibroblast growth factor gene expression in AIDS-Kaposi's sarcoma detected by in situ hybridization.
Biopsy samples from five acquired immune deficiency syndrome (AIDS)-Kaposi's sarcomas and one non-AIDS-associated Kaposi's sarcoma were assayed by in situ RNA hybridization onto paraformaldehyde-fixed, paraffin-embedded skin sections for the presence of two fibroblast growth factor gene transcripts, FGFB and FGF5. FGF5 gene expression was detected in the characteristic Kaposi's sarcoma spindle-shaped cells in the five samples from human immunodeficiency-positive (HIV+) patients. FGFB transcripts were detected in Kaposi's sarcoma cells as well as in epidermis of HIV- and HIV+ patients. These results complement the observations about growth factor gene expression done on Kaposi's sarcoma-derived cell lines, which thus appear to be representative of what happens in vivo. Furthermore, they demonstrate a contrasting expression pattern of FGF5 and FGFB genes, both involved in the growth factor pathogenic cascade leading to Kaposi's sarcoma.
[Prognostic value of the cellular expression of carcinoembryonic antigen (CEA) in gastric adenocarcinoma].
Fifty resected gastric adenocarcinomas were studied retrospectively to evaluate survival factors. Eleven different criteria were assessed using multivariate analysis. Only two criteria were significant: 1--cellular expression of carcinoembryonic antigen (p less than 0.0001 - CCR = 1.48) 2--intravascular or lymphatic tumor emboli (p less than 0.006 - CCR = 2.06). Thus, it is suggested that in addition to the various prognostic factors available to the surgical pathologist, the presence of cellular expression of carcinoembryonic antigen in tumor tissue will aid in predicting the prognosis of patients with gastric carcinoma.
Distribution of estrogen and progesterone receptors in healthy tissue adjacent to breast lesions at various stages--immunohistochemical study of 107 cases.
The purpose of this study was to determine the distribution of ER+ (estrogen receptor) and PR+ (progesterone receptor) epithelial cells in normal mammary tissue or in tissue in contact with or involved in benign or malignant processes. Three important findings emerged from this study. First, a true dissociation was observed between ER+ and PR+ cells in mammary tissue. In premenopausal women some cells express only progesterone receptors. In premenopausal normal tissue, regardless of the menstrual cycle status, 6% of cells are ER+ and 29% PR+. Second, during the menstrual cycle the percentage of positive cells varies. This finding would indicate a change in cell recruitment rather than in intracellular levels. Finally, specific changes in the proportion of positive cells in normal tissue in contact with epithelial proliferations were noted. This finding suggests the possibility of either a diffusible factor or a cellular pathological process spreading beyond areas displaying morphological changes.