Worse histological grade of proximal colorectal tumors and its relation with stage.

PURPOSE: Accumulated data seem to support the concept that proximal and distal colorectal cancers (CRC) should be considered as different disease entities. We investigated a particular aspect of this assumption by examining variation of stage and grade distribution according to tumor site in a Greek patients' group. METHODS: A total of 200 cases having had undergone surgery for primary CRC was retrospectively analysed. Fifty-seven proximal tumors were compared to 143 distal lesions regarding tumor stage (TNM I-IV) and grade of differentiation (well, moderate and poor). Grade distribution by site was also examined within each particular stage and within additional stage categories (I-II, III-IV, I-III, II-IV, II-III). RESULTS: There was an almost significant trend of distal tumors for earlier stage (I) presentation (p=0.055), whereas proximal cancers were more frequently diagnosed with stages II-III (p=0.08). Poorly differentiated lesions displayed a strong predilection for proximal site (p=0.002), while tumors with moderate differentiation were preferentially found distally (p=0.001). Such segmental differences in grade distribution were also ascertained within most particular stages and all additional stage subsets (especially the last three). Moreover, both the proximal and the poorly differentiated lesions showed a parallel decrease in their incidence during the study period. CONCLUSION: The consistently recorded worse histological pattern of proximal tumors implies a different biological behavior of these lesions possibly due to distinct tumorigenic pathways involved in their development, whereas their tendency for late stage presentation demands further investigation before considered supportive to this concept.

Site impact on colorectal cancer biological behavior in terms of clinicopathological and molecular features.

PURPOSE: We investigated the biological behavior of proximal and distal colorectal adenocarcinomas (CRC), intending to determine specific segmental differences, possibly arising from the distinct genetic pathways involved in their development. METHODS: Thirty-six proximal and 83 distal cancers were comparatively and retrospectively analyzed, regarding tumor stage, grade and Ki-67, p53 and Bcl-2 immunohistochemical expression. RESULTS: Proximal tumors were more likely to be poorly differentiated (p=0.005) and to exhibit low Ki-67 and p53 expression (<20% and ≤ 30% stained nuclei respectively; p=0.026 and 0.0014, respectively). Distal lesions were more likely to be moderately differentiated (p=0.001), to display moderate Ki-67 expression (20-50% stained nuclei, p= 0.013) and p53 staining higher than 30% stained nuclei (p= 0.0014). Such segmental variations regarding mainly p53 and to a lesser extent Ki-67 were seen within most of the specific sub-groups of patients (stratified by stage, grade, gender and age). An association between Bcl-2 expression and distal site was also observed among females (p=0.008). CONCLUSION: Proximal and distal cancers displayed different clinicopathological and molecular patterns, reinforcing the proposal that they are genetically and biologically different entities. Potential clinical applications of these findings should be investigated.

Germ line mutation analysis in families with multiple endocrine neoplasia type 2A or familial medullary thyroid carcinoma.

The RET proto-oncogene has been identified as the multiple endocrine neoplasia type 2 disease gene. An association between specific RET mutation and disease phenotype has been reported. We present the phenotype-genotype of 12 Greek families with multiple endocrine neoplasia type 2A (MEN 2A) or familial medullary thyroid carcinoma (FMTC). Seventy members were studied and DNA analysis for RET mutations was performed in fifty-eight of them. Exons 10, 11, 13, 14 and 16 of the RET proto-oncogene were analyzed by single strand conformation polymorphism analysis, direct DNA sequencing and/or restriction enzyme analysis. No mutations of the RET proto-oncogene were identified in 1 of 9 families with MEN 2A and in the 3 families with FMTC. In 7 MEN 2A families, the mutation was demonstrated in codon 634 and in 1 family it was demonstrated in codon 620. There was a low frequency, about 8%, of hyperparathyroidism associated with MEN 2A. The specific causative mutations for pararthyroid disease were C634R or C634Y. Among the MEN 2A individuals there was one case with de novo C634R mutation and one case, C634Y, with cutaneous lichen amyloidosis which predated by 24 years the diagnosis of MEN 2A. In 2 children who were MEN 2A gene carriers, microscopic medullary thyroid carcinomas were found. These data show a low frequency of hyperparathyroidism in our cases and provide further evidence that individuals with C634R as well as with C634Y mutations of the RET proto-oncogene could be at risk for parathyroid disease. Cutaneous lichen amyloidosis could be an early feature of MEN 2A. Additionally, direct DNA testing provided an opportunity to resect medullary thyroid carcinoma at an early stage.

K-ras oncogene mutations in neoplasias of kidney transplanted patients: preliminary results with a new technique.

K-ras oncogene activations by point mutations are frequent in many forms of human cancers but there is a special category of cancers occurring in immunosuppressed patients after kidney transplantation in which the frequency of K-ras oncogene activation has not been fully studied. We used a new sensitive and easy method for the detection of this mutation, and in 8 DNA samples studied from various neoplasias of 8 patients after kidney transplantation, we found 4 mutations. Our preliminary results indicate that the activation of K-ras oncogene at codon 12, is a common event among the kidney transplanted patients who present a neoplasia, even in the least aggressive forms of the disease, contrary to the sporadic cases.

Morphological-histochemical study of intestinal carcinoids and K-ras mutation analysis in appendiceal carcinoids.

Intestinal carcinoids are potentially malignant neoplasms. Their histogenesis and pathogenesis are currently uncertain. The morphological and histochemical characteristics of twenty intestinal carcinoids are studied. The primary sites of three mucin-producing tumors were examined by electron microscope. Furthermore 11 appendiceal carcinoids were analysed by the polymerase chain reaction (PCR) for the detection of ras and p53 point mutations. Microscopically all carcinoids were of mixed type. Focal mucin production was evident in three carcinoids that metastasised to regional lymph nodes. HID-Alcian blue staining proved that mucin in both primary and secondary foci did not belong to the sulphated group. The secretory granules and mucin droplets found in a single neoplastic cell suggest that carcinoids of the small intestine and some of the appendix arise from the endoderm. Neither ras nor p53 mutations were detected. It seems that ras oncogenes are probably not involved in the pathogenesis of appendiceal carcinoids.

Findings of computerised nuclear morphometry of papillary thyroid carcinoma in correlation with known prognostic factors.

The aim of this study was the evaluation of the usefulness of nuclear morphometry in the pathology of papillary thyroid carcinoma by computer-aided image analysis and the statistical comparison of nuclear morphometric parameters with age of patients, tumor size and the presence or not of thyroid capsule invasion. Thirty three cases of papillary thyroid carcinoma were classified in two groups according to patients' age (group I: < 45 years and group II: > 45 years), according to tumor's size (group I: < 2.5 cm, group II: > 2.5 cm) and to the presence or not of thyroid capsule invasion (group I: invasion (+), group II: no invasion (-)). The following six nuclear morphometric parameters were measured in a large number of randomly selected nuclei of each case: area, perimeter, major axis length, minor axis length, elongation and roundness. The statistical analysis was performed using special algorithms and the results of the two groups of each prognostic factor examined, were compared for each of the measured parameter using the t-test. When the classification was associated with age it was shown that younger people (group I) have lower area, perimeter, major axis length, elongation and roundness means of papillary thyroid carcinoma nuclei than older ones (group II) whereas minor axis length did not show any difference between the two groups. When the classification was associated with tumor size it was shown that younger people (group I) have lower area, perimeter, major axis length means of papillary thyroid carcinoma nuclei than older ones (group II) whereas minor axis length, elongation and roundness did not show any difference between the two groups. Finally, when the cases were classified according to the presence or not of the capsule invasion it was shown that younger people (group I) have lower area, perimeter, major axis length means of papillary thyroid carcinoma nuclei than older ones (group II) whereas roundness did not showed any difference between the two groups. On the other hand younger people (group I) have higher elongation and roundness means than the older ones (group II). Nuclear morphometry in association with the patients' follow-up could represent an important prognostic index for papillary thyroid carcinoma.

Imaging and localization of pancreatic insulinomas.

For pancreatic insulinomas, the treatment of choice is surgical excision, which when successful is curative. Intraoperative palpation combined with ultrasonography theoretically depict almost all tumors, however the accuracy of palpation is improved by the preoperative localization. All recent advances in imaging have improved the likelihood for curative surgical resection. Our purpose is to demonstrate the characteristics of all modalities, which may be used in the preoperative localization algorithm.

[Clear cells of the endometrium: an indicator of estrogen level]. / Die "hellen Zellen" des Endometriums: Ein Indikator auf den Ostrogenspiegel.

We examined 70 cases of curettage (24 in normal proliferative phase and 46 with endometrial hyperplasia) and determined the percentage of clear cells among all glandular cells. The number of clear cells was increased in endometrium with hyperplasia without atypia or with minimal atypia (Grade of the endometrial hyperplasia I-IV. Classification of Hendrickson and Kempson 1979). It decreased as the hyperplasia became more severe. Besides we noticed an increase of clear cells in late proliferative phase. The relation of clear cells to estrogen level has been discussed.

Monocyte production in Hodgkin's disease and non-Hodgkin's lymphoma.

Monocytopoietic proliferation activity was investigated in patients with untreated Hodgkin's disease, Hodgkin's disease in long-term complete remission, and untreated non-Hodgkin's lymphoma of the lymphosarcoma and reticulosarcoma type. Untreated Hodgkin's disease was found to be associated with a rise in medullary monocyte production which returned to normal during long-term complete remissions. In contrast, monocyte production was increased in only 5 out of 14 patients with lymphosarcoma and reticulum cell sarcoma, normal in 3, and reduced in 6. In neither of these lymphomas was any relation between monocyte production and stage or histology of the disease detectable.

Findings of computerized nuclear morphometry of papillary thyroid carcinoma in correlation with the age of the patients.

The aim of this study was to evaluate the usefulness of nuclear morphometry in the pathology of papillary thyroid carcinoma by computer-aided image analysis and the statistical comparison of nuclear morphometric parameters with the age of patients. Seventy cases of papillary thyroid carcinoma diagnosed by fine needle aspiration (FNA) biopsies were classified into two groups according to the patients' age (group I: <45 years and group II: >45 years). The following six nuclear morphometric parameters were measured in a large number of randomly selected nuclei of each case: area, perimeter, major axis length, elongation, roundness, and compactness. The statistical analysis was performed by using special algorithms, and the results of the two groups were compared for each of the parameters measured using the t-test. Area, perimeter, and major axis length of papillary thyroid carcinoma nuclei demonstrate a statistically significant correlation with the age of patients, whereas elongation, roundness, and compactness did not show any correlation. Nuclear morphometry in association with the follow-up of patients could be suggested as an important prognostic index for papillary thyroid carcinoma.