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PubMed2005

Coxsackie and adenovirus receptor promotes adenocarcinoma cell survival and is expressionally activated after transition from preneoplastic precursor lesions to invasive adenocarcinomas.

PURPOSE: The cell adhesion protein, coxsackie and adenovirus receptor (CAR), is differentially expressed in various human adenocarcinomas. We analyzed the role of differential CAR expression during tumorigenesis and in cell survival of adenocarcinomas. EXPERIMENTAL DESIGN: In a murine mammary cancer model, a syngenic preneoplastic mammary tissue was implanted into the mammary fat pads of syngenic female BALB/c mice. CAR expression was determined by semiquantitative reverse transcription-PCR in the preneoplastic noninvasive precursor lesions and the developing invasive adenocarcinomas. Cell clones overexpressing CAR were generated and tested for their response to apoptotic factors and for the expression of apoptosis relevant proteins by reverse transcription-PCR and Western blot analysis. RESULTS: In comparison of preneoplastic precursor lesions with established adenocarcinomas, CAR expression was enhanced 2- to 5-fold in all six tissues which had survived and transformed into invasive adenocarcinomas. When stable CAR-overexpressing cell clones of the human cancer cell lines HeLa, CaSki, and A2780 were compared with the parental cell lines, 1.5- to 6-fold more cells survived application of tumor necrosis factor-related apoptosis-inducing ligand or growth factor withdrawal. CAR-enhanced cell survival was accompanied by reduced activation of caspase 3 and enhanced expression of bcl-2 or bcl-XL, depending on the cell type tested. Up-regulation of bcl-2 was found in all CAR-expressing adenocarcinomas of the murine cancer model. CONCLUSIONS: CAR expression is enhanced after transition from preneoplastic precursor lesions to neoplastic mammary cancer outgrowths. Enhanced CAR expression can promote cancer cell survival. These data suggest differential expression of CAR as a new factor in tumorigenesis.

Adenocarcinoma↗
PubMed1995

p53 mutation without allelic loss and absence of mdm-2 amplification in a transplantable hamster pancreatic ductal adenocarcinoma and derived cell lines but not primary ductal adenocarcinomas in hamsters.

An investigation of p53 gene mutation by single-stranded conformation polymorphism analysis of polymerase chain reaction products followed by direct sequencing and of murine double minute 2 (mdm-2) gene amplification by Southern blot analysis was performed, using a series of hamster pancreatic duct adenocarcinomas: 18 primary adenocarcinomas induced by N-nitrosobis(2-oxopropyl)amine, a transplantable adenocarcinoma (HPD), and three cell lines derived from HPD (HPD1NR, HPD2NR, and HPD3NR). A mutation in the p53 gene was detected at codon 197, resulting in an amino acid change from leucine to phenylalanine, in both HPD and the three cell lines but in none of the 18 primary adenocarcinomas. In the three HPD cell lines, which were confirmed to contain only cancer cells, a normal p53 gene allele was retained. Immunohistochemical investigation of p53 expression using polyclonal antibody Ab-7 revealed positive nuclear staining in the HPD and two back-transplanted tumors derived from HPD1NR and HPD2NR but not in the 18 primary adenocarcinomas. mdm-2 gene amplification was not detected in 18 primary adenocarcinomas or any of the tumor cell lines. The results suggest that a p53 gene mutation without allelic loss, together with overexpression of p53 protein, may be a genetic alteration involved in the progression stage of multistep pancreatic carcinogenesis in hamsters and that mdm-2 gene amplification is not important for this process.

Animals↗
PubMed1983

Metastasis of bronchogenic adenocarcinoma to renal adenocarcinoma.

Metastasis of bronchogenic adenocarcinoma to renal adenocarcinoma occurred in a 79-year-old woman. The bronchogenic adenocarcinoma metastasized widely to various organs, whereas the renal adenocarcinoma was nonmetastatic. This case brings the total reported number of cancer-to-cancer metastases to 37. Renal adenocarcinoma was the recipient in 24, and bronchogenic carcinomas comprised one half of all donor cancers.

Adenocarcinoma↗
PubMed2005

Sinonasal tubulopapillary low-grade adenocarcinoma: a specific diagnosis or just another seromucous adenocarcinoma?

Histopathologically, sinonasal adenocarcinomas fall into four categories: the intestinal type, the conventional salivary gland type (eg, adenoid cystic carcinoma, acinic cell carcinoma), the seromucous type, and the low-grade not otherwise specified type. Recently, a new type of sinonasal adenocarcinoma has been described, called tubulopapillary low-grade adenocarcinoma. In this commentary, the histologic features of this type of tumor are compared with those of the other types of sinonasal adenocarcinoma. The clinicopathologic characteristics and probable origin of this type of adenocarcinoma are also discussed.

Adenocarcinoma↗
PubMed2004

Usefulness of Cdx2 in separating mucinous bronchioloalveolar adenocarcinoma of the lung from metastatic mucinous colorectal adenocarcinoma.

We studied the diagnostic value of Cdx2 to distinguish mucinous bronchioloalveolar carcinoma from mucinous colorectal adenocarcinoma metastatic to the lung. We retrieved 92 via the hospital computer system, including 30 mucinous bronchioloalveolar carcinomas, 32 nonmucinous bronchioloalveolar carcinomas, and 30 mucinous colorectal adenocarcinomas metastatic to the lung. All cases were confirmed by clinical history and surgical resection with occasional immunohistochemical studies. Cases were stained with antibodies against Cdx2, thyroid transcription factor-1 (TTF-1), cytokeratin (CK) 7, and CK20. Bronchioloalveolar carcinoma, mucinous type, showed positive staining for Cdx2, TTF-1, CK7, and CK20 in 0 (0%), 5 (17%), 30 (100%), and 18 (60%) of 30 cases, respectively; nonmucinous tumors were positive in 0 (0%), 30 (94%), 32 (100%), and 0 (0%) of 32 cases, respectively. For colorectal adenocarcinoma, the positive staining for Cdx-2, TTF-1, CK7, and CK20 was 29 (97%), 0 (0%), 7 (23%), and 29 (97%) of 30 cases, respectively. Our results demonstrated Cdx2 as a sensitive and specific marker for differentiating metastatic colorectal adenocarcinoma from mucinous bronchioloalveolar adenocarcinoma.

Adenocarcinoma↗
PubMed1999

Cytologic features of villoglandular adenocarcinoma of the uterine cervix: comparison with typical endocervical adenocarcinoma with a villoglandular component and papillary serous carcinoma.

BACKGROUND: To the authors' knowledge, the cytologic features of villoglandular adenocarcinoma (VGC) have been described in very few publications. The malignant cells are difficult to separate from reactive glandular cells and the majority of VGCs are missed on screening cytology. METHODS: The cytologic findings of a retrospective study of four cases of pure VGC are described and are contrasted with those of papillary serous adenocarcinoma and typical mucinous endocervical adenocarcinoma with a focal component of VGC. RESULTS: Although atypical glandular cells of endocervical origin were reported when the smears from the VGC cases were examined in the screening program, none of the cases was recognized as malignant prior to histologic diagnosis. The smears showed many groups of endocervical glandular cells. Important architectural features included large cohesive groups and sheets of cells showing nuclear crowding and loss of the normal honeycomb pattern. True papillary structures comprising stromal cores covered by well polarized columnar cells with a smooth surface were characteristic. It is important to note that a "feathered edge" appearance of the cell groups was absent. The neoplastic cells were mildly atypical, showing a slight increase in the nuclear-cytoplasmic ratio but minimal hyperchromatism. The cytology smears of four cases of typical adenocarcinoma of endocervical type that had a focal VGC pattern showed cell groups with irregular borders and "feathered" edges comprised of distinctly atypical columnar cells with elongated and irregular hyperchromatic nuclei. Free-lying atypical cells and ball-like clusters of atypical cells also were present in the latter cases but not in pure VGCs. The primary high grade papillary serous adenocarcinomas of the cervix exhibited extreme cytologic atypia that was interpreted readily as malignant. CONCLUSIONS: The diagnosis of VGC on cytology smears often is missed. Papillary fragments, nuclear crowding, and subtle atypia may suggest the diagnosis.

Adenocarcinoma, Papillary↗
PubMed1984

Adenocarcinoma in situ and invasive adenocarcinoma of the uterine cervix. An immunohistologic study with antibodies specific for several epithelial markers.

The distribution of carcinoembryonic antigen (CEA), secretory component (SC), fat globule membrane antigens ( FGMA ), and keratin was determined immunohistochemically in 22 invasive adenocarcinomas of various types and in 9 adenocarcinomas in situ of the uterine cervix. In the invasive adenocarcinomas 77% were positive for CEA, 47% for SC, 89% for keratin, and 77% for FGMA . In adenocarcinomas in situ 67% were positive for CEA, 11% for SC, and 44% for keratin. The location of the markers was variable in the cells, and the cells in a tumor were irregularly positive. For a given histologic type there were several phenotypes. No correlation was found between histologic types of invasive adenocarcinomas and the various phenotypes. It remains to be shown whether a particular phenotype has a particular biological behavior. The detection in the serum of the markers shown in histologic preparations could be useful in the postsurgical monitoring.

Adenocarcinoma↗
PubMed1994

The observation of angiogenin and basic fibroblast growth factor gene expression in human colonic adenocarcinomas, gastric adenocarcinomas, and hepatocellular carcinomas.

Using digoxigenin-labelled, synthetic oligonucleotide probe cocktails of angiogenin and bFGF genes, the expression of the two genes was observed by in situ hybridization in ten colonic adenocarcinomas, seven gastric adenocarcinomas, and four hepatocellular carcinomas. The angiogenin gene was expressed in eight of the ten cases of colonic adenocarcinoma and in all of the four cases where dysplastic glands were found. Angiogenin expression was evident in four of the seven cases of gastric adenocarcinoma. bFGF expression was detected in only five of the seven gastric carcinoma cases. The mRNAs for angiogenin and bFGF were mainly cytoplasmic in distribution and were only occasionally seen in the nuclei of the positive cells. Neither the angiogenin gene mRNA nor the bFGF mRNA was expressed in the four cases of hepatocellular carcinoma. It is postulated that the angiogenin gene may play an important role in angiogenesis in colonic adenocarcinomas; in gastric cancers, both angiogenin and bFGF were involved in this process. For hepatocellular carcinomas, neither angiogenin nor bFGF production appeared to be related to angiogenesis.

Adenocarcinoma↗
PubMed2000

Recurrent invasive adenocarcinoma after hysterectomy for cervical adenocarcinoma in situ.

BACKGROUND: Unlike its squamous counterpart, therapy for cervical adenocarcinoma in situ with positive endocervical cone margin remains controversial. CASE: A 52-year-old gravida 2, para 1,0,1,1, presented with vaginal bleeding. Gynecologic history was significant for cervical cold knife conization with a positive endocervical margin and endocervical curettage with atypical endocervical cells. Repeat cone biopsy was considered unsafe given the large initial cone specimen. An extrafascial hysterectomy was performed 5 weeks later and pathology confirmed a disease-free cervix. Pap smear performed 1 year later was interpreted as recurrent adenocarcinoma but later downgraded to inflammation. Inspection and random biopsies of the vaginal cuff revealed only inflammation. Two subsequent Pap smears also returned inflammation. Seventeen months after the hysterectomy physical examination revealed a 2 x 3-cm smooth mass at the vaginal cuff. Biopsy revealed invasive adenocarcinoma. The patient underwent an upper vaginectomy followed by postoperative pelvic radiation. CONCLUSION: This case suggests that despite extrafascial hysterectomy for presumed adenocarcinoma in situ of the cervix, a residual focus could remain and present later as invasive adenocarcinoma.

Adenocarcinoma↗
PubMed2002

Infrared spectral features of exfoliated cervical cells, cervical adenocarcinoma tissue, and an adenocarcinoma cell line (SiSo).

OBJECTIVE: The objective of the present study is to evaluate and compare the infrared spectral features of normal and malignant exfoliated cervical cells, cells from malignant tissue, and the SiSo cell line. METHODS: Infrared spectra of cervical adenocarcinoma (CA) tissue, normal and malignant exfoliated cervical cells, and a uterine cervical adenocarcinoma cell line (SiSo) were obtained. Spectral qualities in terms of band intensity ratio and band position, which reflect configurational changes in the functional groups of the above samples, were measured. RESULTS: Spectral bands of CA tissue, exfoliated cells from CA, and the cell line were similar but markedly different from that of exfoliated normal cervical cells. Significant changes in bands at 1025 cm(-1) (glycogen), 1080 cm(-1) (glycogen and nucleic acids), 1155 cm(-1) (C-OH groups of serine, threonine, and tyrosine of cell proteins, and C-O groups of carbohydrates), 1240 cm(-1) (PO(2) groups of nucleic acids), 1400 cm(-1) (methyl group of lipids and proteins), and 1450 cm(-1) (methylene group of lipids and proteins) were noted in the CA tissue, exfoliated CA cells, and adenocarcinoma cell line compared with exfoliated normal cells. Marked shifts in band positions from 1080 to 1086 cm(-1), 1153 to 1160 cm(-1), and 935 to 970 cm(-1) in CA tissue, exfoliated CA cells, and the adenocarcinoma cell line were noted. CONCLUSION: Spectral bands of the adenocarcinoma cell line matched very well with those of cervical CA tissue and exfoliated CA cells in terms of position. In contrast, spectral bands of the SiSo cell line differed greatly from those of normal exfoliated cells.

Adenocarcinoma↗
PubMed2002

Adenocarcinoma of the upper esophagus arising in heterotopic gastric mucosa: common pathogenesis with Barrett's adenocarcinoma?

Adenocarcinoma of the upper esophagus arising in heterotopic gastric mucosa is a rare tumor, with only 15 cases reported to date. We report a case in a 61-year-old man complaining of dysphagia. The upper endoscopy revealed that the tumor measured 3 cm and was 22 cm distant from the incisivors. A hiatal hernia with erosive esophagitis of the distal esophagus was present. On microscopic examination the tumor corresponded to a poorly differentiated adenocarcinoma immunoreactive for cytokeratin (CK) 7 and p53. The surrounding heterotopic gastric mucosa contained foci of intestinal metaplasia immunoreactive for CK7 in the surface epithelium and the entire glands and CK20 in the superficial epithelium and superficial glands. The CK7 and p53 positivity that we observed is very common in Barrett's adenocarcinomas. Moreover, intestinal metaplasia in heterotopic gastric mucosa shows the same CK7/CK20 pattern as specialized Barrett's mucosa. These common features shared by adenocarcinomas of the upper esophagus arising in heterotopic gastric mucosa and adenocarcinoma of the lower esophagus developing on Barrett's mucosa suggest that those two types of cancer have a common pathogenesis, related to gastroesophageal reflux disease.

Adenocarcinoma↗
PubMed2005

Pelvic sidewall adenocarcinoma after definitive therapy for cervical adenocarcinoma in situ.

BACKGROUND: Traditionally, hysterectomy is considered definitive therapy for cervical adenocarcinoma in situ (AIS) in women beyond childbearing. CASE: A 45-year-old gravida 2, para 2 patient presented with cervical dysplasia and on pathology review of the large loop excision procedure cervical adenocarcinoma in situ was diagnosed. She underwent extrafascial hysterectomy and bilateral salpingo-oophorectomy. Final pathology revealed adenocarcinoma in situ with negative margins. Twenty-eight months later, she presented with right lower extremity deep venous thrombosis. A computed tomography (CT) scan of the abdomen and pelvis showed a pelvic sidewall mass. A CT-guided biopsy of the mass was consistent with invasive adenocarcinoma of the endocervical type. She underwent combination therapy with weekly cisplatin and extended field radiation therapy. CONCLUSION: This case depicts another example of the unpredictable nature of cervical AIS. Despite undergoing definitive surgery, a residual focus of disease may remain leading to invasive adenocarcinoma. Close follow-up is required of all patients diagnosed with AIS because the disease is poorly understood.

Adenocarcinoma↗
PubMed2004

[Ovarian adenocarcinoma, primary or metastasic tumour of an adenocarcinoma of the colon: the role of molecular biology].

After the primary diagnosis of an adenocarcinoma, diagnosis of the origin of a second adenocarcinoma is a problem (primitive or metastatic). Although the clinical evolution or location sometimes makes it possible to determine the origin of the new lesion, in some cases the diagnosis cannot be confirmed. Although a pathological examination is essential for diagnosis, it may still be inconclusive, making management difficult. The use of molecular biology can help solve this problem. We report the case of a patient who presented with an ovarian adenocarcinoma of an undetermined origin one year after an adenocarcinoma of the colon. This clinical case illustrates the contribution of molecular biology in the diagnosis of the origin of an ovarian adenocarcinoma by characterizing allelic losses in 5 chromosome segments using microsatellite markers genotyping in the two lesions. The comparative analysis suggested the primitive origin of the ovarian lesion.

Adenocarcinoma↗
PubMed2000

Aggressive digital papillary adenocarcinoma (aggressive digital papillary adenoma and adenocarcinoma revisited).

In 1987 a clinicopathologic study by the Armed Forces Institute of Pathology (AFIP) of rare sweat gland tumors, termed aggressive digital papillary adenoma and adenocarcinoma, was published. Since that time, the AFIP has continued to collect these tumors for study. Based on additional follow-up data, we think the original classification of these tumors requires revision. Sixty-seven cases of aggressive digital papillary adenoma and adenocarcinoma were studied according to their clinical characteristics and histologic features. Fifty of these were originally diagnosed as adenoma and 17 as adenocarcinoma. Follow up on 45 (67%) of the patients was obtained. None of the clinical or histologic parameters studied were found to be predictive of recurrence or metastasis, indicating that the originally proposed criteria for distinguishing between benign (adenoma) and malignant (adenocarcinoma) do not predict biologic behavior. When primary tumors were treated by subsequent reexcision or amputation, only one recurred (5%), when not so treated, 11 recurred (50%) regardless of the original diagnosis (p <0.05). Metastasis occurred in six (14%) cases and in three cases led to the death of the patient. Three of these metastatic cases had met the earlier criteria for adenoma. Pulmonary metastases were observed in five cases. No effective treatment for widespread metastatic disease has yet been developed. Because histologic features with prognostic significance could not be demonstrated in this retrospective review, we propose that all aggressive digital papillary tumors be designated aggressive digital papillary adenocarcinoma.

Adenocarcinoma, Papillary↗
PubMed1995

Monoclonal antibodies Ki-67 and MIB1 in the distinction of tuboendometrial metaplasia from endocervical adenocarcinoma and adenocarcinoma in situ in formalin-fixed material.

This study was undertaken to determine whether immunostaining with the monoclonal antibodies Ki-67 and MIB1 is of use in the distinction of tuboendometrial metaplasia from endocervical adenocarcinoma and adenocarcinoma in situ (AIS) on formalin-fixed, paraffin-embedded tissue. Tissue sections from 100 cases (52 normal endocervix, 27 endocervical tuboendometrial metaplasia, eight endocervical AIS, 13 endocervical adenocarcinoma) were stained with Ki-67 and MIB1 after microwave pretreatment in citrate buffer. Ki-67 and MIB1 labelling indices (LIs) were calculated in each case by determining the percentage of positive-staining nuclei. Five hundred nuclei were counted in each case. Significant differences in Ki-67 and MIB1 LIs existed between the adenocarcinoma group and the tuboendometrial metaplasia group and between the AIS group and the tuboendometrial metaplasia group. No significant differences existed between the adenocarcinoma and AIS groups. Over all groups, the Ki-67 LI was consistently lower than the MIB1 LI. The results indicate that immunohistochemical staining with Ki-67 and MIB1 may be of use in the often difficult histological distinction of tuboendometrial metaplasia from malignant endocervical glandular lesions.

Adenocarcinoma↗
PubMed2004

Immunohistochemical screening for beta6-integrin subunit expression in adenocarcinomas using a novel monoclonal antibody reveals strong up-regulation in pancreatic ductal adenocarcinomas in vivo and in vitro.

AIMS: To analyse the expression of alphavbeta6, an epithelial integrin involved in wound healing and tumorigenesis, in various human carcinoma types. METHODS AND RESULTS: A new monoclonal antibody to the human beta6 subunit, 5C4, was used to locate alphavbeta6 in 157 cancers of gastroenteropancreatic and 21 of lung origin. The data were validated by analysis of alphavbeta6 extracted from histological sections. Alphavbeta6 integrin showed strongest expression in 34 pancreatic ductal adenocarcinomas (mean score 2.88 +/- 0.52), followed by 24 intestinal-type gastric carcinomas (1.45 +/- 1.06) and eight lung adenocarcinomas (1.37 +/- 1.1). Moderate expression was found in 31 diffuse-type gastric carcinomas (0.94 +/- 0.83), seven duodenal adenocarcinomas (0.8 +/- 1.34) and 26 colorectal adenocarcinomas (0.76 +/- 0.71). Little alphavbeta6 was seen in seven liver cell carcinomas and six neuroendocrine tumours. Well-differentiated carcinomas expressed more beta6 than poorly differentiated tumours. Peritumoral epithelial tissues where alphavbeta6-expressing tumours arose also expressed alphavbeta6. There was no correlation between expression of alphavbeta6 and its ligands tenascin and fibronectin in pancreatic and gastric carcinomas. Spheroid formation by pancreatic carcinoma cell lines led to alphavbeta6 up-regulation, but appeared independent of classical ligand binding to alphavbeta6. CONCLUSIONS: Our findings indicate that: (i) alphavbeta6 is overexpressed in pancreatic adenocarcinomas; (ii) alphavbeta6-positive carcinomas originate from alphavbeta6-expressing tissues; (iii) alphavbeta6 expression in tumours seems to be regulated independently from that of its ligands tenascin and fibronectin; and (iv) in-vitro overexpression of alphavbeta6 in pancreatic carcinoma cell lines accompanies spheroid formation.

Adenocarcinoma↗
PubMed1997

Adenocarcinoma of the cervix and adenocarcinoma of the endometrium: distinction with PCR-mediated detection of HPV DNA.

The differential diagnosis between primary endocervical adenocarcinoma and adenocarcinoma originating in the endometrium may in some cases be difficult. The two cancer types have a different genesis, with human papillomavirus (HPV) as an important causal factor in the development of primary cervical carcinoma. In this study, the paraffin-embedded cervical tissues from 23 patients with stage II endometrial carcinoma and from 50 patients with primary cervical adenocarcinoma were examined for HPV DNA of types 16, 18, and 33. HPV DNA was demonstrated in 70% of the primary endocervical adenocarcinomas and in none of the endometrial carcinomas. It is concluded that HPV detection may be useful in the differential diagnosis of some cases of cervical and endometrial adenocarcinoma.

Adenocarcinoma↗
PubMed2006

Immunohistochemical distinction of intestinal-type sinonasal adenocarcinoma from metastatic adenocarcinoma of intestinal origin.

OBJECTIVES: Distinction of intestinal-type sinonasal adenocarcinoma (ITAC) from adenocarcinoma of intestinal origin metastatic to the sinonasal cavity may be extremely difficult on histologic grounds alone. We studied the role of cytokeratin (CK) and mucin (MUC) expression in differentiating ITAC, metastatic adenocarcinoma of intestinal origin, and non-intestinal-type sinonasal adenocarcinoma (non-ITAC). METHODS: We stained specimens from 5 cases of ITAC and 4 cases of non-ITAC, along with 4 colonic and 3 duodenal adenocarcinoma controls, with CK7 and CK20, MUC2 and MUC5, neuron-specific enolase (NSE), chromogranin (CHR), and carcinoembryonic antigen (CEA) in order to examine the possible combinations of markers that best aid in the diagnosis of these lesions. We also performed a retrospective review of our clinical experience with these rare lesions. RESULTS: CK7 staining was positive in all ITAC and non-ITAC cases, whereas all cases displaying gastrointestinal-type differentiation (ITAC and metastatic intestinal cases) stained positive for both CK20 and MUC2. Staining for MUC5, NSE, CHR, and CEA was variable. CONCLUSIONS: Tumors with the CK7+, CK20+, MUC2+ immunophenotype are likely primary sinonasal lesions, whereas tumors with the CK7-, CK20+, MUC2+ profile warrant further clinical evaluation to exclude metastatic disease from the gastrointestinal tract. Complete surgical resection of ITAC remains the mainstay of therapy.

Adenocarcinoma↗