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At least 19 recordsLinked to original sources

FIGO stage, histology, histologic grade, age and race as prognostic factors in determining survival for cancers of the female gynecological system: an analysis of 1973-87 SEER cases of cancers of the endometrium, cervix, ovary, vulva, and vagina.

The prognostic impact of FIGO stage, histology, histologic grade, age and race in survival for cancers of the female gynecological (cervix, endometrium, ovary, vulva, vagina) were examined using cases obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program that were diagnosed between 1973 and 1987. Utilizing Cox proportional hazards modeling and relative survival rates analysis of 17,119 cases of cervical cancer indicated that the International Federation of Gynecology and Obstetrics (FIGO) stage, histology, histological grade, lymph node status, and age at diagnosis were all independently prognostic. No evidence was found of survival differences between squamous cell carcinoma and adenocarcinoma. Younger women were not found to have a poorer prognosis, survival declined with increased age. Analysis of 41,120 cases of endometrial cancer indicated that FIGO stage, histology, histologic grade, lymph node status, age at diagnostic, and race were all prognostic factors. Clear cell adenocarcinoma, leiomyosarcoma, and mixed mullerian tumors were all found to have poorer prognosis. Analysis of 21,240 cases of ovarian cancer indicated that FIGO stage, histology, histologic grade, lymph node status, age at diagnosis, presence of ascites, and race were all prognostically significant. Analysis of 2,575 cases of vulvar cancer indicated that FIGO stage, histology, histologic grade, age, and race were all prognostically significant. Analysis of 916 cases of vaginal cancer indicated that FIGO stage, histologic grade, lymph node status, and age are all prognostically significant. Additional analysis of the data by combinations of independent prognostic factors indicates that the interaction of factors may be more predictive of outcome than any one factor separately.

Adenocarcinoma↗

Analysis of histological heterogeneity in renal cell carcinoma: tumor size-related histological change and its prognostic significance.

BACKGROUND: It is well recognized that the histology of renal cell carcinoma (RCC) is often heterogeneous. It is also believed that the prognosis of patients with large tumors is generally poorer than those with small tumors. However, there has been no detailed study on changes in histological features of RCCs associated with tumor growth. This study was conducted to investigate whether there are any specific histological changes related to tumor size and to study the prognostic value of histological parameters in RCCs. METHODS: The presence or absence of each histological component (3 cell types and 5 histological architectures) was investigated in 110 RCCs. The tumor size-associated changes in the histological composition of the RCCs were evaluated, and the prognostic significance of the histological parameters was analyzed using univariate and multivariate analysis. RESULTS: The percentage of RCCs with multiple cell types increased with tumor size, whereas increases in multiplicity were not as prominent in the histological architectures. Several characteristic changes, however, were observed in both cell types and architectures. RCCs with a pure clear cell, pure alveolar pattern or cystic architectural pattern decreased, while those with granular or spindle/pleomorphic cell types, or papillary or solid architectural patterns increased with tumor size. A univariate analysis revealed that a clear cell type and an alveolar or cystic architectural pattern were associated with a better prognosis, while spindle/pleomorphic cells and a solid architecture pattern correlated with a poorer prognosis. Multivariate analysis of cell types and architectures showed, however, that only the presence of spindle/pleomorphic cell types and a solid architecture were independent prognostic variables. CONCLUSION: The histological composition of RCCs varied according to the size of the tumor. Sarcomatous components increased with tumor size and were independently associated with a poor prognosis. Further study is warranted to correlate specific genetic alterations with tumor growth-related histological changes in RCCs.

Adult↗

In vivo model of histologic changes after treatment with the superpulsed CO(2) laser, erbium:YAG laser, and blended lasers: a 4- to 6-month prospective histologic and clinical study.

BACKGROUND AND OBJECTIVE: To compare the in vivo histologic effects of the pulsed carbon dioxide (CO(2)) and erbium:ytrium aluminum garnet (Er:YAG) lasers and to assess the effects of combining CO(2) and Er:YAG laser modalities during a single treatment session. We previously reported 10 patients treated with four laser regimens: CO(2) alone, CO(2)/Er:YAG, Er:YAG alone, Er:YAG/CO(2) with time points at 1 hour and 7 days between laser treatment and histologic analysis. This study found that the optimal treatment consisted of limited CO(2) laser passes followed by Er:YAG. This treatment produced less collagen injury, less thermal necrosis, and more robust epithelial and dermal fibrous tissue regeneration in the acute phase of healing. The present study examines the histologic changes resulting from the host healing response to laser treatment on long-term follow-up of 4-6 months. STUDY DESIGN/MATERIALS AND METHODS: The Stanford University Committee on Human Subjects in Medical Research approved this study. Nine patients with actinic damage and indications for rhytidectomy volunteered for this interventional study in which each patient served as both experimental and control. The right preauricular area was treated at five sites with the following: (1) CO(2), (2) CO(2) followed by Er:YAG, (3) Er:YAG, (4) blended CO(2)/Er:YAG (Derma-Ktrade mark), (5) phenol. Each was subjected to full-face or sub-unit treatment. Each patient was followed up initially daily then weekly for healing of the full-face laser and for differences in healing of the five treatment areas. Five patients were selected for histologic evaluation. At 4-6 months, these patients underwent rhytidectomy with immediate removal of laser-treated skin, which was evaluated histologically by the study dermatopathologist, who was blinded to the treatment at each site. RESULTS: CO(2) laser treatment produced the greatest thickness of neocollagen (0.27 mm; P < 0.05), the highest neocollagen density (P < 0.05), the greatest decrease in elastosis (27%), but took the longest time for healing and resolution of erythema and inflammation (up to 6 months). Er:YAG used alone produced the least collagen density, with the thinnest band of neocollagen (0.08 mm), but the most rapid resolution of erythema and inflammation (within 10 days). Combined CO(2)/Er:YAG treatments, including Derma-Ktrade mark and CO(2) followed by Er:YAG produced histologic changes that were intermediate, as well as recovery that was intermediate (resolution of erythema within 1 month); the development of neocollagen was greater in CO(2)-containing modalities than Er:YAG used alone by a statistically significant margin (P = 0.001). These histologic findings were corroborated by clinical correlation by examination of the five treatment spots in nine patients and in full-face treatments in 100 patients. CONCLUSION: Collagenesis is greatest with CO(2) and least with Er:YAG. Elastosis decreased to the greatest degree with CO(2), least with erbium, and to an intermediate extent with blended CO(2)/Er:YAG regimens (sequential and Derma-K). These changes from control are statistically significant with all regimens (P < 0.05). Blended CO(2)/Er:YAG treatments provide an optimal combination of the benefits of CO(2) but with lesser erythema and healing delay. Clinical and histologic findings change over time for different treatments. Thus, long-term histology is critical for predicting results of treatment.

Algorithms↗

Non-Hodgkin's lymphoma in children; diffuse lymphoblastic histology; diffuse non-lymphoblastic histology; LSA2-L2 experience.

The majority of the patients with non-Hodgkin's lymphoma present with extensive disease at diagnosis. Extranodal is the most common primary site and Non-lymphoblastic histology is the most common histological subtype in pediatric lymphomas of which diffuse histiocytic is certainly the most common of the group, second only to diffuse lymphoblastic histology. Certain histological subtypes are associated with certain primary sites. The LSA2-L2 has been shown in this group to be as effective for lymphoblastic lymphoma as for non-lymphoblastic lymphomas, a slightly lower disease-free survival is due to the fact that, in this group, certain factors such as initial central nervous system involvement, initial bone marrow involvement, and high serum lactic dehydrogenase levels seem to play an important role in prognosis. The comparison of the disease-free survival for the two major subgroups, lymphoblastic and non-lymphoblastic shows the following: For primary intra-abdominal disease, in which clearly the majority belong to the Non-lymphoblastic histology, with a total of 50 patients, the disease-free survival was 67%; for lymphoblastic histology with 5 patients, the actuarial disease-free survival was 100%. For primary mediastinal with 24 patients with diffuse lymphoblastic histology the disease-free survival was 95%, and in 13 patients with Non-lymphoblastic histology a disease-free survival of 83%.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗

Achievement of superior survival for histologically negative versus histologically positive clinically complete responders to cisplatin combination in patients with locally advanced head and neck cancer.

In a series of three consecutive pilot studies conducted between 1977 and 1982 at Wayne State University, Detroit, Michigan, 191 consecutive patients with previously untreated, locally advanced head and neck cancer were treated with cisplatin (CDDP), vincristine, and bleomycin or CDDP and 5-fluorouracil (5-FU) infusion before definite surgery or radiation. A 39% (75/191) rate of complete clinical responses was achieved. Thirty-two of the chemotherapy-induced complete responders underwent radical surgery. Thirteen had no histologic evidence of residual disease in the surgically resected specimen. The CDDP and 5-FU infusion combination achieved the highest histologic complete response rate. All histologically complete responders who had completed local radiation therapy are clinically free of disease at median follow-up of 36 months. Patients who achieved complete response both clinically and histologically had superior survival as compared to patients who achieved complete response clinically and were subsequently found to have residual tumor in their surgically resected specimen (P = 0.01). An analysis of the clinical and pathological pretreatment characteristics was performed to identify factors predictive of histologic complete response. Advanced nodal disease correlated inversely with the achievement of negative histology in the surgically resected specimen (P = 0.02). No other factors were significant in predicting response.

Adult↗

Histological esophagitis: clinical and histological response to omeprazole in children.

Many children with esophagitis demonstrate histological changes without gross evidence of esophagitis by esophagoscopy. The effect of omeprazole on the histological healing of esophagitis in children is unknown. Therefore, the aim of this study was to determine the effect of omeprazole on refractory histological esophagitis in pediatric patients. Eighteen patients with histological evidence of esophagitis and recurrent symptoms despite therapy with H2-receptor antagonists and prokinetic agents were prospectively treated with omeprazole. Dosing was adjusted by monitoring intragastric pH, and esophagoscopy was repeated after 8-12 weeks of omeprazole treatment. Two patients did not complete the study due to either worsening symptoms or hypergastrinemia. Of the remaining patients, 76% were asymptomatic with omeprazole treatment and 24% reported improvement in their symptoms. Approximately 40% demonstrated complete histological healing of their esophagitis. Three patients (17%) had persistent elevations in serum gastrin levels while on omeprazole treatment, which was associated with both younger patient age and higher omeprazole dosing; however, all elevated gastrin levels returned to normal after discontinuation of the medication. All patients had recurrence of their symptoms after completing a course of omeprazole, even patients with complete histological healing. Omeprazole is efficacious in treating children with esophagitis refractory to H2-receptor antagonist and prokinetic agents. However, none of the patients were able to discontinue acid suppressive therapy even after documented healing of their esophagitis.

Adolescent↗

Histologic types of lung carcinoma and related family history of anatomic sites and histologic types of cancers.

BACKGROUND: Familial factors are suggested to play roles in lung carcinogenesis, but may well be different for each histologic cell type. METHODS: Information regarding smoking, past medical history, and family history of malignant diseases among first-degree relatives was collected from a total of 1188 patients with primary lung carcinoma (participants) who were treated in the thoracic oncology ward at the National Cancer Center Hospital, Tokyo, Japan. These data were analyzed for associations with the histologic type of the lung carcinoma. The main outcome measures were the relative risk of developing a malignancy, at any site or at certain specific sites, in first-degree relatives of participants who had a specific histologic type of lung carcinoma compared with the relative risk in those first-degree relatives of participants with other cell types. RESULTS: Participants with multiple malignant lesions reported significantly more first-degree relatives with a malignancy than those without multiple tumors (P = 0.008 by the Wilcoxon rank sum test). There was no statistically significant correlation between age, gender, smoking history, or histologic tumor type in the participant and the overall family history of malignancy. Site specific analyses revealed that participants with adenocarcinoma reported a family history of colorectal carcinoma, and those with squamous cell carcinoma reported a family history of head and neck carcinoma, more frequently than other participants (P = 0.041 and 0. 001, respectively, by chi-square analysis). CONCLUSIONS: The data from the current study suggest an association between familial factors and histologic type of lung carcinoma. Genetic factors to determine individual susceptibility to lung carcinogenesis should be investigated according to each histologic type.

Adenocarcinoma↗

The evolution of spondyloarthropathies in relation to gut histology. II. Histological aspects.

OBJECTIVE: To study prospectively the clinical evolution of different forms of spondyloarthropathy (SpA) in relation to the type of gut histology in ileocolonoscopic biopsy specimens. METHODS: Ileocolonoscopy was performed in 217 patients with SpA (149 men, 68 women). Three types of gut histology (normal gut histology and acute and chronic inflammatory gut lesions) were found. Clinical, laboratory, and radiological examinations were performed at start and 2 to 9 years later in 123 patients who were regularly monitored. For the remaining 94 patients clinical data were obtained by telephone. RESULTS: Of the 123 patients monitored regularly, 40 (32%) had normal gut histology, and 28 (23%) had acute and 55 (45%) chronic inflammatory gut lesions. Acute lesions were preferentially found in patients with non-ankylosing spondylitis SpA (non-AS-SpA). In the groups with normal gut histology and with chronic gut inflammation, patients with ankylosing spondylitis (AS) and non-AS-SpA were present in equal numbers. At review, clinical evolution was identical in the 3 histological subgroups. Eight patients developed idiopathic inflammatory bowel disease (IBD), one with initially acute gut inflammation, 7 with initially chronic gut inflammation. All had active AS at review. Fourteen patients with non-AS-SpA developed AS; 13 of them had initially presented inflammatory gut lesions. Three patients in the telephone group also developed IBD; all had active AS at review and initially presented chronic inflammatory gut lesions. Persistently high inflammatory serum variables, HLA-B27 negativity in the presence of sacroiliitis or AS, and inflammatory gut lesions at the first ileocolonoscopy indicate patients with SpA are at risk for developing IBD. CONCLUSION: Gut inflammation, mainly subclinical, could be demonstrated in 68% of patients with SpA. Acute gut inflammation was predominant in patients with reactive arthritis (ReA). The evolution to clinical remission was not influenced by the presence or the type of gut inflammation at start. Patients with non-AS-SpA with inflammatory gut lesions have greater risk of developing AS. One patient with Yersinia induced ReA developed AS and IBD. In total, 11 patients (66%) developed IBD, all initially presenting inflammatory gut lesions. Ten had chronic gut lesions, suggesting this type of gut inflammation is related to the inflammation of Crohn's disease. This type of gut inflammation, the persistence of high inflammatory serum variables, and the absence of HLA-B27 in patients with AS are risk factors for developing IBD.

Adolescent↗

Functional comparative histology. 1. Communication: comparative and functional aspects of histology.

Comparative histology demonstrates the different ways through which a function can be performed by one or more structures. The functional approach offers the widest comparison, much wider than any morphologic comparison would be able to do. The function adds the physiological and biochemical approach to the picture. Histochemistry bridges the gap between both, the comparative and functional aspect, as well as tissue and organ culture. The tissues show a variation in their phylogenetic age of appearance and taxonomic distribution. Comparative functional histology is a basic science of the various biological disciplines. Comparative functional histology is also a basic pillar of experimental pathology. The functional frame of comparative histology has been outlined. The following communications of the series listed below will give a detailed description of special aspects of comparative functional histology.

Animal Population Groups↗

Relative and total volume of histological components in benign prostatic hyperplasia: relationships between histological components and clinical findings.

To investigate the correlation between histological differences and clinical findings in patients with benign prostatic hyperplasia (BPH), quantitative morphometrical analysis on prostate was performed on 26 specimens obtained by TURP. The relative and total volume of each histological component were obtained. In this series, the proportion of fibrous tissue element showed a weak positive correlation with prostatic volume (r = 0.499, P = 0.0087). The relative volume of the smooth muscle component showed an inverse correlation with prostatic volume (r = -0.488, P = 0.0105). Patient age and symptom score showed no relationship with the relative volume of histological components. The total volume of all histological components increased with prostatic volume. However, an increase in the fibrous tissue element appeared to be predominant in prostatic enlargement (r = 0.970, P < 0.0001). Although the total volume of all histological components increased with prostatic size, fibrous tissue appeared to play a major role in prostatic enlargement in BPH.

Aged↗

The relationship between premedical coursework in gross anatomy and histology and medical school performance in gross anatomy and histology.

Many premedical students enroll in courses whose content will be encountered again during their medical education. Presumably, students believe this practice will lead to improved academic performance in corresponding medical school courses. Therefore, this study was undertaken to determine whether a premedical gross anatomy and/or histology course resulted in increased performance in corresponding medical school courses. A second aim of the study was to examine whether the type of premedical gross anatomy and/or histology course differentially affected medical school performance. A survey that assessed premedical gross anatomy and histology coursework was administered to 440 first-year medical students. The results from this survey showed that students with premedical gross anatomy (n = 236) and/or histology (n = 109) earned significantly more points in the corresponding medical school course than students without the premedical coursework (P < 0.05). Analysis of premedical course types revealed that students who took a gross anatomy course with prosected specimens (n = 35) earned significantly more points that those students without premedical gross anatomy coursework (P < 0.05). The results from this study suggest: 1) premedical gross anatomy and/or histology coursework improves academic performance in corresponding medical school courses, and 2) a premedical gross anatomy course with prosected specimens, a specific type of undergraduate course, significantly improves academic performance in medical gross anatomy.

Adult↗

Neoadjuvant chemotherapy for high-grade central osteosarcoma of the extremity. Histologic response to preoperative chemotherapy correlates with histologic subtype of the tumor.

BACKGROUND: In primary central high-grade osteosarcoma, a number of distinct subtypes have been identified, but little is known about the response to chemotherapy. METHODS: The authors investigated whether the subtypes correlated with histologic response to chemotherapy in 1058 patients with osteosarcoma of the extremities who were treated with neoadjuvant chemotherapy over the last 20 years. The tumors were classified as osteoblastic (70%), chondroblastic (13%), fibroblastic (9%), and telangiectatic (6%). At diagnosis, 911 patients had localized disease and 147 had resectable lung metastases. RESULTS: The response to preoperative chemotherapy was good (90% or more tumor necrosis) in 59% of patients and poor (< 90% tumor necrosis) in 41% of patients. The rate of good responses was significantly higher (P = 0.0001) in the fibroblastic (83%) and telangiectatic (80%) tumors and significantly lower in chondroblastic tumors (43%). Prognosis was significantly correlated with the histologic subtypes. The 5-year overall survival rate was significantly higher (P = 0.0001) in fibroblastic (83%) and telangiectatic (75%) tumors than in osteoblastic (62%) and chondroblastic (60%) tumors. In all subtypes, except for the chondroblastic subtype, the 5-year overall survival rate was significantly higher (P = 0.0001) in good responders P = 0.0001 (68%) than in poor responders (52%). CONCLUSIONS: The authors concluded that the histologic subtype of primary central high-grade osteosarcoma of the extremity was strictly correlated with histologic response to chemotherapy and probably, as a consequence, also with prognosis. Further studies are needed to establish whether these results justify a specific therapeutic approach based on the histologic subtype of the tumor.

Adolescent↗

Mild abnormalities in liver histology associated with chronic hepatitis: distinction from normal liver histology.

BACKGROUND: Chronic hepatitis C virus infection associated with contaminated anti-D immunoglobulin has become an issue of recent concern. The clinical course of chronic hepatitis C infection is unpredictable and histological assessment is felt to be the most reliable means of assessing disease status. Semiquantitative scoring systems have been devised, which assess degree of necroinflammatory disease activity (grade) and extent of disease progression with fibrosis (stage) in chronic hepatitis. Often, using these systems, biopsies of anti-D associated chronic hepatitis C cases show mild changes only, with low scores. The significance of these low scores is uncertain. AIMS: To evaluate the significance of low scores in chronic hepatitis. METHODS: Liver biopsies were assessed from two groups of patients in whom liver histology would be expected to be normal: 30 cases of Gilbert's syndrome and 13 necropsy cases of young people (< 45 years) with no history or risk factors for liver disease. These biopsies were scored using the histological activity index of Knodell et al and its recent modification (separation of scores for grade and stage) by Ishak et al. RESULTS: Twenty of 30 cases of Gilbert's syndrome and 11 of the 13 necropsy cases had chronic hepatitis scores of 1 or 2, whereas only eight cases of Gilbert's and two necropsy cases had scores of 0. The remaining two Gilbert's cases had scores of 3 and 5. Similar results were found using both the histological activity index of Knodell et al and the method of Ishak et al. CONCLUSION: The finding of low but positive scores using these systems in people with normal liver histology questions the reliability and significance of finding such scores in patients with chronic hepatitis and is of particular concern in the evaluation of chronic hepatitis C infection.

Adult↗

[Measurement of serum immunoreactive beta-glucuronidase: a possible serological marker for histological hepatic cell necrosis and to predict the histological progression of hepatitis].

beta-Glucuronidase, a lysosomal hydrolase, was purified from human liver tissue, and an enzyme-linked immunosorbent assay was developed using specific antibody against the enzyme. Using the assay procedure, the serum immunoreactive beta-glucuronidase (beta-glucuronidase) was determined in 190 patients with various liver diseases and in 53 healthy controls to examine whether or not the serum level of beta-glucuronidase would successfully reflect the degree of histological hepatic cell necrosis. beta-Glucuronidase was also determined at regular intervals in 28 patients with chronic hepatitis to investigate the clinical usefulness of serial measurement of the enzyme to predict the histological progression of hepatitis. These 28 patients could be subdivided into three groups, "continuously low type", "labile type" and "elevated type" according to the profiles of fluctuation of serum beta-glucuronidase values. Serum beta-glucuronidase was significantly increased in patients with hepatoma, liver cirrhosis and chronic active hepatitis compared with normal controls. There was significant positive correlation between the beta-glucuronidase and the degree of hepatic cell necrosis determined by histological observation, on the other hand, there was no statistical correlation between the transaminase activities and the degree of hepatic cell necrosis. It was confirmed in immunohistochemical study that the increased beta-glucuronidase in serum has been released from necrotic hepatic cells into blood stream. It was speculated that the elevation of serum transaminase activities had resulted from the alteration in the membrane permeability of hepatic cells rather than from hepatocellular necrosis. Histological progression of hepatitis was found in 8 of 10 patients (80%) of "labile" and "elevated type", while it was found only 3 of 18 patients (16.7%) of "continuously low type". These results suggested that the serial measurement of beta-glucuronidase could be used for an indicator to predict the histological progression of hepatitis.

Carcinoma, Hepatocellular↗

[Clinical and histological features of acute post-transfusion non-A, non-B hepatitis: histological diagnosis in acute stage and clinical outcome].

We have retrospectively studied the clinical and histological features of 55 cases of acute post-transfusion non-A, non-B hepatitis. Histological findings in the liver biopsies taken in the acute stage covered the whole spectrum of acute and chronic hepatitis, the incidence of acute hepatitis or non-specific reactive hepatitis was 12.7% and 16/4%, respectively, while that of chronic active hepatitis was 56.4%. There was no correlation between histological features in acute stage and the mean peak levels in serum alanine aminotransferase (ALT). Post-transfusion hepatitis, non-A, non-B with histological signs of chronic hepatitis in acute stage frequently results in biochemical evidence of chronic liver disease during long-term follow-up periods. Therefore, our results suggest that the histological features of chronic hepatitis in the acute stage are indicative of long-term elevation in serum ALT level.

Acute Disease↗

[Comparative histological analysis of needle biopsy specimens, prostatectomized specimens and metastatic lymph nodes in prostatic adenocarcinoma--on the basis of the WHO histological classification].

The histological characteristics were comparatively analyzed among biopsy specimens, surgically removed prostates and metastatic lymph nodes obtained from 60 patients with prostatic adenocarcinoma treated by radical prostatectomy. According to the WHO-Mostifi's classification, the proportion of the 6 histologic components, large and/or small simple glands (LSG), micro-glands (MIC), cribriorm (CRB), fused glands (FUS), medullary/solid (MED) and columns-cords/trabecular (C-C), was determined semiquantitatively. LSG, MIC, and CRB are androgen-sensitive components, while FUS, MED and C-C are androgen-refractory components. The proportions of 5 histologic components excluding MIC were similar in the biopsy and prostate specimens. In 78.3% of the patients, the presence (or absence) of androgen-refactory components in the biopsy specimens coincided with that in the prostate specimens. However, the histologic except for the C-C component. Metastatic lymph nodes contained androgen-refactory components in all cases and tended to have more CRB and FUS and fewer LSG. The histology of the needle biopsy specimens may reflect that of the prostate glands, and may serve as a valuable parameter for determining therapeutic modalities. In addition, androgen-refactory components are frequently present in lymph node metastasis.

Adenocarcinoma↗

The role of histological investigation in prognostic evaluation of advanced gastric cancer. Analysis of histological structure and molecular changes compared with invasive pattern and stage.

The relative contribution of tumour histology or molecular changes, compared with invasion pattern or stage, to prognostic assessment of gastric cancer was investigated in a series of 185 advanced (T2 to T4, stage IB to IV) cancers that had undergone intentionally curative surgery at Varese General Hospital. Survival analysis of the histological types considered in commonly used classifications, such as Lauren, Kubo, the World Health Organization (WHO) and related classifications, allowed separation of a small high-grade (Hg, 12 cases) group of adenosquamous, anaplastic and small cell endocrine carcinomas from a large cohesive group (C, 86 glandular or solid cancers) and from another large (87 cases) group of tumours with dissociated cells [29 diffuse (D) and 58 mixed (M) tumours]. Univariate and multivariate analysis showed the independent prognostic value of this C/M+D/Hg classification approach, which proved superior to other classifications and to cell dissociation at the growing front or angio, lympho and neuro-invasion. Expression of sialyl Lewis(c), the DUPAN-2 antigen, proved to be an independent predictor of worse survival among tumours beyond stage I, showing an exclusively or predominantly cohesive structure. Microsatellite instability (MSI) predicted favourable survival in purely cohesive tumours of intermediate (II) stage, especially of solid/medullary and lymphoid stroma/lympho-epithelioma-like structure, among which two distinct tumour subsets were characterised, one MSI-positive and the other Epstein-Barr virus positive. T2NOM0 (stage IB) tumours showed mostly favourable survival independently from histological type, invasive pattern, DUPAN-2 or MSI status. It is concluded that an appropriate histological evaluation, coupled with sialylated glycoproteins histochemistry and, for stage-II tumours, MSI tests may contribute significantly to prognostic assessment of tumours beyond stage I. However, the stage itself, with special reference to lymph-node metastases and invasion level beyond subserosa, remains the most important prognostic clue for gastric cancer.

Adenocarcinoma↗