Mucinous Content Research Articles

Comparison of microsatellite instability and chromosomal instability in predicting survival of patients with T3N0 colorectal cancer

Background. At least 2 apparently independent mechanisms, microsatellite instability (MSI) and chromosomal instability, are implicated in colorectal tumorigenesis. Their respective roles in predicting clinical outcomes of patients with T3N0 colorectal cancer remain unknown. Methods. Eighty-eight patients with a sporadic T3N0 colon or rectal adenocarcinoma were followed up for a median of 67 months. For chromosomal instability analysis, Ki-ras mutations were determined by single-strand polymerase chain reaction, and p53 protein staining was studied by immunohistochemistry. For MSI analysis, DNA was amplified by polymerase chain reaction at 7 microsatellite targets (BAT25, BAT26, D17S250, D2S123, D5S346, transforming growth factor receptor II, and BAX). Results. Overall 5-year survival rate was 72%. p53 protein nuclear staining was detected in 39 patients (44%), and MSI was detected in 21 patients (24%). MSI correlated with proximal location (P <.001) and mucinous content (P <.001). In a multivariate analysis, p53 protein expression carried a significant risk of death (relative risk = 4.0, 95% CI = 1.6 to 10.1, P =.004). By comparison, MSI was not a statistically significant prognostic factor for survival in this group (relative risk = 2.2, 95% CI = 0.6 to 7.3, P =.21). Conclusions. p53 protein overexpression provides better prognostic discrimination than MSI in predicting survival of patients with T3N0 colorectal cancer. Although MSI is associated with specific clinicopathologic parameters, it did not predict overall survival in this group. Assessment of p53 protein expression by immunocytochemistry provides a simple means to identify a subset of T3N0 patients with a 4-times increased risk for death. (Surgery 2002;131:190-7.)

Immunocytochemical demonstration of the secretory dynamics of zymogenic contents in rat gastric gland processed by high-pressure freezing/freeze substitution, with special references to phospholipase A(2) and phospholipase Cgamma1.

High-pressure freezing/freeze substitution followed by Lowicryl K4M embedding provided an excellent morphology and antigenicity of the gastric glands, as well as the intraluminal fluid contents. Taking advantage of this, we histochemically investigated the secretory dynamics of the zymogenic contents in rat gastric gland, with special references to phospholipase A(2) (PLA(2)) and phospholipase Cgamma1 (PLCgamma1). The combination of immunogold labeling and KMnO4-uranyl acetate-lead citrate staining for zymogenic contents clearly demonstrated the rapid diffusion of PLA(2) molecules from the exocytosed zymogenic contents into the mucinous contents in gastric glandular lumens. In contrast, the exocytosed PLCgamma1 molecules remained within the zymogenic contents in the glandular lumens. These findings indicated the distinction between the exocytosed PLA(2) and PLCgamma1 in their diffusion rate. In addition, the mucinous contents surrounding the exocytosed zymogenic contents were intensely labeled with Griffonia simplicifolia II lectin which specifically recognizes the mucin of mucous neck cells. Interestingly, some of the PLA(2) immunolabeling on the mucinous contents was associated with the apical membranes of gastric epithelial cells, especially that of parietal cells. The secretory dynamics of the zymogenic contents in rat gastric glands, including their interaction with the mucinous contents are discussed.

Dukes B colorectal cancer: distinct genetic categories and clinical outcome based on proximal or distal tumor location.

The aim of this study was to determine whether tumor location proximal or distal to the splenic flexure is associated with distinct molecular patterns and can predict clinical outcome in a homogeneous group of patients with Dukes B (T3-T4, N0, M0) colorectal cancer. It has been hypothesized that proximal and distal colorectal cancer may arise through different pathogenetic mechanisms. Although p53 and Ki-ras gene mutations occur frequently in distal tumors, another form of genomic instability associated with defective DNA mismatch repair has been predominantly identified in the proximal colon. To date, however, the clinical usefulness of these molecular characteristics remains unproven. A total of 126 patients with a lymph node-negative sporadic colon or rectum adenocarcinoma were prospectively assessed with the endpoint of death by cancer. No patient received either radiotherapy or chemotherapy. p53 protein was studied by immunohistochemistry using DO-7 monoclonal antibody, and p53 and Ki-ras gene mutations were detected by single strand conformation polymorphism assay. During a mean follow-up of 67 months, the overall five-year survival was 70 percent. Nuclear p53 staining was found in 57 tumors (47 percent), and was more frequent in distal than in proximal tumors (55 vs. 21 percent; chi-squared test, P < 0.001). For the whole group, p53 protein expression correlated with poor survival in univariate and multivariate analysis (log-rank test, P = 0.01; hazard ratio = 2.16; 95 percent confidence interval = 1.12-4.11, P = 0.02). Distal colon tumors and rectal tumors exhibited similar molecular patterns and showed no difference in clinical outcome. In comparison with distal colorectal cancer, proximal tumors were found to be statistically significantly different on the following factors: mucinous content (P = 0.008), degree of histologic differentiation (P = 0.012), p53 protein expression, and gene mutation (P = 0.001 and 0.01 respectively). Finally, patients with proximal tumors had a marginally better survival than those with distal colon or rectal cancers (log-rank test, P = 0.045). In this series of Dukes B colorectal cancers, p53 protein expression was an independent factor for survival, which also correlated with tumor location. Eighty-six percent of p53-positive tumors were located in the distal colon and rectum. Distal colon and rectum tumors had similar molecular and clinical characteristics. In contrast, proximal neoplasms seem to represent a distinct entity, with specific histopathologic characteristics, molecular patterns, and clinical outcome. Location of the neoplasm in reference to the splenic flexure should be considered before group stratification in future trials of adjuvant chemotherapy in patients with Dukes B tumors.

Intracranial Abscess with Unusual MR Features

Characterization of necrotic intracranial masses by means of computed tomography and magnetic resonance is always difficult. The pre and post contrast aspects and morphological characteristics of the solid component could suggest diagnosis, but in many cases they are not specific. In unusual cases, the necrotic central tissue could have the specific aspect of MR and CT signals (metastasis with mucinous material or rich in melanin), but generally it is not possible to characterize the lesion with this parameter, because it does not present specific features (hypodensity on CT, hyperintensity on PD and T2-weighted MR images, hypointensity on T1-weighted scans). The case that we describe regards an intracranial abscess with necrotic material presenting a high signal in all sequences. These signal characteristics are typical of tissue with a high mucinous content, so we assume that in this case the hyperintensity on T1-weighted images is due to proteic material from granulocyte lysis.

Lymphoepithelial cyst of the pancreas

Compared to pseudocyst formation after prior pancreatitis, true cysts of the pancreas are rare. Pancreatic cysts with irregular wall components or a mucinous content raise the suspicion for the presence of a cystic neoplasm, and surgical resection is recommended. A case of a patient with a history of prostate cancer is described in whom a cyst of the pancreatic tail was discovered incidentally. Based on the radiographic features, which did not support the presence of a serous cystadenoma, a spleen-preserving distal pancreatectomy was performed. Histologic features were characteristic for a lymphoepithelial cyst (LEC) of the pancreas, lined with thinned squamous epithelium surrounded by benign lymphoid tissue. Since LECs of the parotid gland, which are associated with acquired human immunodeficiency, are frequently related to Epstein-Barr virus (EBV) infection, EBV in situ hybridization was performed and did not reveal evidence for EBV. Twenty-eight instances of pancreatic LECs have been reported, primarily affecting adult males, without evidence of increased numbers of EBV-positive cells. The pathogenesis, differential diagnosis, and clinical implications of lymphoepithelial pancreatic cysts are discussed.

Simple mucin-type Tn and sialosyl-Tn carbohydrate antigens in salivary gland carcinomas

Neoplastic transformation is associated frequently with changes in the glycosylation process. Simple mucin-type glycosylation in cancer cells has been found to be characterized by incomplete synthesis with precursor accumulation, leading to the exposure of the structures Tn and sialosyl-Tn, which are normally cryptic in human cells and secretions, including saliva and salivary glands. Paraffin sections from 50 salivary gland carcinomas of different histologic types were investigated with immunohistologic studies and a panel of monoclonal antibodies with well-defined specificity for Tn and sialosyl-Tn. Tn and sialosyl-Tn antigens were expressed in the cytoplasm of glandular differentiated cells; in the luminal membranes and mucinous content of the glandular differentiated areas in almost all mucoepidermoid carcinomas and adenocarcinomas; and in carcinoma in pleomorphic adenoma, when the malignant component was an adenocarcinoma. In contrast, acinic cell carcinomas and adenoid cystic carcinomas expressed only minimal amounts of Tn and sialosyl-Tn, and the staining was seen only in relation to the luminal membrane and mucin of a few glandular structures. Mucin-type Tn and sialosyl-Tn may be regarded as markers of a glandular differentiation pattern in salivary gland carcinomas. The cellular location of the antigen-antibody complex indicates that they are synthesized and secreted from the tumor cells into saliva or serum.

Necrotizing Squamous/Mucinous Metaplasia in Oncocytic Salivary Gland Tumors: A Potential Diagnostic Problem

Tumor necrosis and squamous and/or mucinous metaplasia was found in 4 of 26 oncocytic salivary gland tumors (24 Warthin's tumors and 2 oncocytomas). The necrosis was extensive in two cases, producing architectural and cytologic atypia sufficient to simulate a squamous carcinoma. In a third tumor, necrotic and inflammatory debris occurred within dilated tumor spaces exhibiting squamous and mucinous foci, suggesting low-grade mucoepidermoid carcinoma. Adequate sampling revealed Warthin's tumors in all four cases. An additional 13 tumors showed incidental foci of squamous metaplasia, often accompanied by stromal scarring but without necrosis. Four of these tumors also had focal mucinous metaplasia. In the adjacent non-neoplastic salivary gland, oncocytic metaplasia of ducts was seen in 22 glands; there were 7 oncocytic cysts and 3 oncocytic nodules. The tumor necrosis and metaplasia are reminiscent of necrotizing sialometaplasia of the minor salivary gland, thought to be ischemic in origin. The etiology of necrotizing squamous/mucinous metaplasia described here and the extent to which oncocytosis contributes to these changes is unknown. Possibly the extravasation of oncocytic and/or mucinous secretions or cyst contents may result in the reactive changes observed. Necrotizing sialometaplasia and squamous/mucinous metaplasia of oncocytic tumors appear to be related only morphologically, but the shared histologic features may be useful in excluding the diagnosis of salivary gland carcinoma.

Survival of patients with ovarian cancer. Apart from stage and grade, tumor progesterone receptor content is a prognostic indicator

Estrogen (ER), progesterone (PR), and androgen receptors (AR) were determined by saturation analysis in 100 cases of primary ovarian cancer and correlated with patient survival. The mean follow-up period was 5.4 years (range, 4 to 6.5 years). Positivity for PR was associated with a significantly better survival rate (P less than 0.05). A similar observation was made for AR (P less than 0.05). Tumor ER content did not correlate with survival. Ten patients with tumors that had negative results for both PR and AR all died of the disease. In 91 cases of serous, endometrioid, and mucinous carcinomas, grade, stage, and tumor PR content, but not AR content, were identified as independent prognostic factors with the use of the Cox proportional hazards model. The relative risk of patients with PR-negative tumors was 2.3 times higher than that of patients with tumors containing high (greater than or equal to 30 fmol/mg) PR levels.

Infantile hypoventilation syndrome, neurenteric cyst, and syringobulbia

Hypoventilation syndrome was observed in an infant with a neurenteric cyst. She died at 9 months of age following episodic bradycardia and the loss of voluntary as well as autonomic respiratory control. There was a mediastinal neurenteric cyst with anterior spina bifida and extension into the upper thoracic spinal cord. Secondary syringomyelobulbia was present at necropsy. The syringobulbia involved the hypoglossal nuclei, the dorsal motor nuclei of the vagus in the lower medulla, the right nucleus ambiguus, the right fasciculus and nucleus solitarius, the right mediolateral reticular formation, and the right dorsal motor nucleus of the vagus at the level of the obex. This morphologic distribution is attributed to the intraspinal rupture and upward extension of the mucinous contents of the cyst, and appears to be responsible for the hypoventilation syndrome.

Histophysiology of the pituitary cleft and colloid cysts in the adenohypophysis of the rat; changes after gonadectomy and adrenalectomy.

SUMMARY 1. Pituitaries of normal, adrenalectomized and castrated male rats have been studied using the freeze-drying technique. 2. The pituitary cleft is surrounded anteriorly by an endothelioid fenestrated epithelium and posteriorly by a cubical or cylindrical epithelium. In the latter colloid droplets can be seen in the cytoplasm, and evaginations containing colloid droplets occur at the apical poles of the cells and project into the lumen of the cleft. 3. The histological picture suggests that the colloid contained in the cleft might be formed by: (a) destruction of the basophilic and eosinophilic cells of the pars distalis, (b) transudation of plasma from capillaries in the anterior wall of the cleft, (c) mucus discharged by goblet cells in the anterior epithelium, and (d) apocrine secretion and the secretion of colloid from the posterior epithelium. 4. Changes in the height, the amount of cytoplasmic colloid and the apocrine secretion of the posterior epithelium occur after adrenalectomy and castration. 5. There are two types of cyst in the adenohypophysis, one having a mucinous content and covered with a mucous epithelium, and the other a flattened epithelium and a colloid content. The latter, in addition to the pituitary cleft, might play some part in secretory processes.