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Abstract

Although pyloric and duodenal adenomas occasionally occur in cats, limited information is currently available on their phenotypes and molecular features. The present study investigated the pathological features of these tumors and the mechanisms underlying their tumorigenesis. Biopsy samples from 8 cats diagnosed with pyloric or duodenal adenomas were examined by histopathology and immunohistochemistry. Normal pyloric and duodenal tissues of cats were assessed for comparison. All cases showed a papillary growth of cuboidal to columnar cells with eosinophilic, ground-glass cytoplasm. Mucin in tumor cells was positive for periodic acid–Schiff and paradoxical concanavalin-A staining, but was negative for Alcian blue. Immunohistochemically, tumor cells were positive for cytokeratin (CK) 19 in 8/8 cases and for CK20 in 5/8 cases, and weakly positive for CD10 in 4/8 cases, CK7 in 3/8 cases, and β-catenin in 2/8 cases. Nuclear accumulation of p53 was not detected in any case. DNA sequencing analysis identified no KRAS or GNAS mutations in the 4/8 cases and 5/8 cases for which the KRAS and GNAS genes could be amplified. The histological and immunohistochemical features of tumor cells were similar to those of mucous neck cells and the pyloric gland of normal feline tissue. The morphology of feline pyloric and duodenal adenomas was consistent with that of pyloric gland adenoma in humans; however, its molecular pathogenesis may differ given the lack of KRAS and GNAS mutations in the feline tumors.

Keywords

cats adenoma stomach duodenum immunohistochemistry surgical pathology

The gastrointestinal tract is the third most frequent organ affected by neoplastic diseases in cats, with more than 80% being malignant.¹⁰ Benign epithelial tumors, such as adenomatous polyps or adenomas of the pyloric and duodenal area, have been reported.^6,18 The gastric and duodenal segment is composed of various types of epithelial cells: foveolar, fundic gland, pyloric gland, intestinal epithelium, intestinal submucosal gland, and pancreatobiliary duct cells (duodenal papilla). However, few histopathological studies have been conducted on pyloric and duodenal adenomas in the cat,⁶ and the phenotypes of these neoplastic epithelial cells have not been examined in detail.

In humans, adenomas in the stomach and duodenum are broadly classified into gastric and intestinal types based on the phenotypes of tumor cells.^8,15 These 2 types of adenoma differ not only in their histological features but also in their molecular pathogenesis. Activating mutations in KRAS are common in both the gastric and intestinal types, whereas GNAS mutations are found only in the gastric type, particularly in pyloric gland adenoma.^11,12,19 However, limited information is currently available on the genetic features, including the KRAS and GNAS mutation status, of feline gastrointestinal tumors,³³ and it has not yet been clarified whether feline pyloric and duodenal adenomas correspond to human gastric- or intestinal-type adenomas.

In the present study, we examined the phenotypes of neoplastic cells in feline pyloric and duodenal adenomas by comparing their morphological, histochemical, and immunohistochemical features with normal epithelial cells comprising the feline gastrointestinal mucosa. The molecular features of tumor tissue, including KRAS and GNAS alterations, were analyzed. The mechanisms underlying the tumorigenesis of feline pyloric and duodenal adenomas are also discussed in comparison with those of human gastrointestinal adenoma.

Materials and Methods

The records of feline gastric and/or duodenal biopsy cases (681 cases) that were submitted to the Laboratory of Veterinary Pathology, the University of Tokyo, between 2009 and 2020 were reviewed. Eight cats histopathologically diagnosed with pyloric and/or duodenal adenoma were selected for further histopathological examinations. Tissue specimens were obtained through endoscopic biopsy or surgical resection. Follow-up information on clinical improvement and survival days were collected through local veterinarians.

All tissues were fixed in 10% neutral buffered formalin and routinely embedded in paraffin wax. Consecutive sections (thickness of 4 μm) were stained with hematoxylin and eosin (HE), Alcian blue (pH 2.5)-periodic acid–Schiff (AB-PAS), and paradoxical concanavalin-A staining (PCS) (which identifies class III mucins characterized by GlcNAcα1 → 4Galβ residue), and immunohistochemistry was performed. The gastric and duodenal tissues of normal cats were also stained with AB-PAS, PCS, and immunohistochemistry for comparison.

For immunohistochemistry, endogenous peroxidase was blocked by a treatment with 3% hydrogen peroxide in methanol for 5 minutes. To unmask antigens, sections were then treated with citrate buffer (pH 6.0) by heating in an autoclave (121 °C) for 10 minutes or were incubated with 125 µg/ml proteinase K (Wako) solution at room temperature for 30 minutes. After washing with Tris-buffered saline (TBS), slides were treated with 8% skimmed milk in TBS. The primary antibodies used are listed in Table 1. After an incubation with primary antibody at 4 °C overnight, immunolabeled antigens were visualized using the Dako Envision+ System (Dako) and reacted with 0.05% 3′,3-diaminobenzidine plus 0.03% hydrogen peroxide in Tris-hydrochloric acid buffer. Sections were then counterstained with hematoxylin. The immunoreactivity of neoplastic cells was scored semiquantitatively as follows: − (negative), <1% positive cells; + (weakly positive), 1% to 30% positive cells; ++ (moderately positive), 31% to 60% positive cells; +++ (strongly positive), >60% positive cells. Nuclear immunoreactivity was interpreted as positive for β-catenin, CDX2, and p53, whereas membranous or cytoplasmic reactivity was interpreted as positive for CD10, CK7, and CK20.

Table 1.

Antibodies used for immunohistochemistry.

Antibody	Type (clone)	Dilution	Supplier	Antigen retrieval
β-catenin	mAb mouse (14/beta-catenin)	1:1000	BD Biosciences	Heat (pH 6)
CD10	mAb mouse (56C6)	Ready to use	BioGenex	Heat (pH 6)
CDX2	mAb mouse (CDX2-88)	Ready to use	BIOCARE	Heat (pH 6)
CK7	mAb mouse (OV-TL 12/30)	1:100	Dako	Proteinase K
CK19	mAb mouse (B170)	Ready to use	Leica	Proteinase K
CK20	mAb mouse (Ks20.8)	1:50	Dako	Proteinase K
p53	pAb rabbit	1:200	Santa Cruz	Heat (pH 6)

Abbreviations: CK, cytokeratin; mAb, monoclonal antibody; pAb, polyclonal antibody.

Genomic DNA was extracted from formalin-fixed paraffin-embedded pyloric and/or duodenal tissues using the QIAamp DNA FFPE Tissue Kit (Qiagen) for gene mutation analysis. Purified DNA was used in subsequent polymerase chain reaction (PCR), in which amplification was conducted with specific primer pairs for the feline KRAS gene that amplifies a 286-bp fragment that incorporates exon 1, 5′-AGGTGAATTTGCGTTAAAAGGTAT-3′ (forward) and 5′-AAAGAATGGGCCTGCACAAA-3′ (reverse), and with specific primer pairs for the feline GNAS gene that amplifies a 441-bp fragment incorporating exons 8 and 9, 5′-CCCTTTCCAAGCTCGTCAGG-3′ (forward) and 5′-AGCAGAAGCAGTGTGGGTTA-3′ (reverse). PCR was performed as follows: for primers for the KRAS gene, 30 cycles at 95 °C for 30 seconds and 53 °C for 30 seconds; for primers for the GNAS gene, 30 cycles at 95 °C for 30 seconds and 61 °C for 30 seconds. PCR products were submitted for a sequence analysis in the forward direction (Eurofins Genomics Inc). Each chromatogram was visually inspected for any abnormalities. Unaffected feline tissue was also used to confirm the normal sequences of the feline KRAS and GNAS genes.

Results

Clinical and Endoscopic Findings

Among 681 feline gastric and/or duodenal biopsy cases, 8 (1.2%) were diagnosed as pyloric and/or duodenal adenoma. Information on each case is summarized in Table 2. Archived samples were obtained from 3 intact males, 3 spayed females and 2 intact males, aged 5 to 13 years (average: 10 years). Cases involved 4 mixed breed, 1 Abyssinian, 1 Birman, 1 Russian Blue, and 1 Scottish Fold. The most common clinical signs were anorexia (6/8 cases), vomiting (5/8 cases), diarrhea (2/8 cases), and weight loss (1/8 case). Intestinal T-cell lymphoma (small-cell type) and severe colitis were also present in 2/8 and 1/8 cases, respectively. Upper gastrointestinal endoscopy was performed on all cases and revealed smooth, round masses within the pylorus or proximal duodenum (Figs. 1, 2). Six cases had a single mass in gastroduodenal junction or duodenum, and the other 2 cases had 2 masses in the stomach and duodenum that were separated from each other (Figs. 1, 2). In case 6, the pyloric mass was pedunculated, smooth and larger than the duodenal mass, whereas the duodenal mass was sessile and multilobulated. In case 8, the pyloric and duodenal masses were both well-demarcated semi-pedunculated, and similar in size. Polyps were removed during endoscopy in 6/8 cases, while laparotomy and surgical resection were performed in 2/8 cases. Improvement of clinical signs was observed after endoscopic or surgical removal in 6/7 cases; however, case 7 developed T-cell lymphoma/leukemia and died 344 days after resection. Case 4 had intestinal lymphoma and died 21 days after the duodenal adenoma was diagnosed. The clinical outcome of case 2 was not available.

Figures 1–2.

Pyloric and duodenal adenoma, cat, case 6. Figure 1. Stomach, pylorus. A broad-based polyp with a smooth surface. Figure 2. Proximal duodenum. A sessile and multilobulated polyp.

Table 2.

Demographic and clinical information on feline pyloric and duodenal adenoma cases.

Case no.	Breed	Age (year)	Sex	Location	Clinical signs	Coexisting disease	Survival days after resection^a	Clinical improvement	Note
1	Mix	5	M	Proximal duodenum	Anorexia, vomiting	None	417 (alive)	Yes
2	Mix	7	SF	Proximal duodenum	Anorexia, vomiting	None	NA	NA
3	Mix	7	SF	Pyloro-duodenal junction	Anorexia, vomiting	None	604 (alive)	Yes
4	Mix	11	CM	Proximal duodenum	Anorexia, diarrhea	Intestinal T-cell lymphoma, small-cell type	21 (died)	No
5	Birman	9	M	Pyloro-duodenal junction	Anorexia	None	1105 (alive)	Yes
6	Scottish Fold	12	CM	Pylorus and duodenum	Weight loss	None	139 (alive)	Yes
7	Abyssinian	13	M	Proximal duodenum	Vomiting, diarrhea	Severe colitis	344 (died)	Yes (diarrhea remained)	Diagnosed with T-cell lymphoma/leukemia 2 months before death
8	Russian Blue	13	SF	Pylorus and duodenum	Anorexia, vomiting	Intestinal T-cell lymphoma, small-cell type	505 (alive)	Yes

Abbreviations: M, intact male; CM, castrated male; SF, spayed female; NA, not available.

^a Survival days after resection: Data available as of May 2021.

Histopathology

All tumors had similar histologic lesions irrespective of the affected site. Tumors were composed of a tubulopapillary arrangement of cuboidal to columnar cells, and tubules were often dilated with a serous component. Tumor cells had abundant, eosinophilic, ground-glass cytoplasm, and round and basally located nuclei with small nucleoli (Figs. 3, 4). Mild anisokaryosis and pseudostratification with loss of polarity were observed (Fig. 4). Mitotic figures were rarely detected. The stroma was composed of fibrous tissue accompanied by mild edema and mild infiltration with lymphocytes and plasma cells. Invasive growth of tumor tissue was not detected in any case.

Figures 3–6.

Pyloric adenoma, stomach, cat, case 6. Figure 3. A tumor with dilated glands arises from the mucosa. Hematoxylin and eosin (HE). Figure 4. Neoplastic cells have an eosinophilic, ground-glass cytoplasm and round nuclei with mild anisokaryosis. HE. Figure 5. Tumor cells contain mucin that is Alcian blue (pH 2.5) (AB)-negative and periodic acid–Schiff (PAS)-positive. AB-PAS. Figure 6. Intracellular mucin is positive for paradoxical concanavalin-A staining.

Histochemistry and Immunohistochemistry

The results of special stains and immunohistochemistry for normal and neoplastic feline gastric and duodenal tissues are summarized in Tables 3 and 4. In the normal gastric and duodenal tissue, AB−/PAS+ mucin was observed in foveolar, fundic gland, pyloric gland, and intestinal submucosal gland cells. AB+/PAS+ or AB+/PAS− mucin was only found in the intestinal epithelium and fundic gland cells, respectively. PCS-positive mucin was also detected in fundic, pyloric, and intestinal submucosal gland cells. Immunolabeling for CD10 and CDX2 was restricted to the intestinal epithelium. CK7 immunoreactivity was also limited to pancreatobiliary ducts, while CK19 immunoreactivity was observed in all epithelial cells, except for intestinal submucosal gland. CK20 immunolabeling was detected in all epithelial cells examined.

Table 3.

Histochemical and immunohistochemical results in normal feline stomach and duodenum.

Cell types	AB-PAS	PCS	CD10	CDX2	CK7	CK19	CK20
Foveolar cell	AB−/PAS+	−	−	−	−	+	+
Fundic gland	AB−/PAS+ (mucous neck cell)AB+/PAS− (chief cell)	+ (mucous neck cell)	−	−	−	+ (mucous neck cell)	+ (mucous neck cell)
Pyloric gland	AB−/PAS+	+	−	−	−	+	+
Intestinal epithelium	AB+/PAS+ (goblet cell)	−	+	+	−	+	+
Intestinal submucosal gland	AB−/PAS+	+	−	−	−	−	+
Pancreatobiliary duct	AB+/PAS+	−	−	−	+	+	+

Abbreviations: AB-PAS, alcian blue (pH 2.5)-periodic acid–Schiff; PCS, paradoxical concanavalin-A staining; CK, cytokeratin.

Table 4.

Histochemical and immunohistochemical results in feline pyloric and duodenal adenomas.

Case no.	Histochemistry		Immunohistochemistry^a
Case no.	AB-PAS	PCS	CD10	CDX2	CK7	CK19	CK20	β-catenin^b	p53^b
1	AB−/PAS+	Positive	+	−	+	++	++	−	−
2	AB−/PAS+	Positive	+	−	+	+++	−	−	−
3	AB−/PAS+	Positive	−	−	−	+++	−	−	−
4	AB−/PAS+	Positive	−	−	−	+	+	−	−
5	AB−/PAS+	Positive	+	−	−	+	−	+	−
6	AB−/PAS+	Positive	+	−	−	+	++	−	−
7	AB−/PAS+	Positive	−	−	+	+++	+++	−	−
8	AB−/PAS+	Positive	−	−	−	++	+	+	−

Abbreviations: AB-PAS, alcian blue (pH 2.5)-periodic acid–Schiff; PCS, paradoxical concanavalin-A staining; CK, cytokeratin.

^a− (negative), <1% positive cells; + (weakly positive), 1% to 30% positive cells; ++ (moderately positive), 31% to 60% positive cells; +++ (strongly positive), >60% positive cells.

^b Nuclear immunoreactivity was interpreted as positive.

Neoplastic cells contained AB-/PAS+ mucin in all cases (Fig. 5). The intracellular mucus and serous components in neoplastic ducts were also predominantly positive for PCS (Fig. 6).

Immunohistochemically, neoplastic cells in all cases were weakly or strongly positive for CK19 (Fig. 7). Tumor cells in 5/8 cases were also positive for CK20 to various degrees (Fig. 8). In 4/8 and 3/8 cases, neoplastic cells were weakly positive for CD10 and CK7, respectively (Figs. 9, 10). Weak nuclear immunolabeling for β-catenin was observed in 2/8 cases (Fig. 11). The nuclear accumulation of p53 was not detected in any case (Fig. 12).

Figures 7–12.

Pyloric and duodenal adenoma, cat. Immunohistochemistry. Figures 7–9. Stomach, case 6. Figure 7. Tumor cells are partly positive for cytokeratin (CK) 19. Figure 8. Tumor cells are diffusely immunolabeled for CK20. Figure 9. A small number of tumor cells are positive for CD10. Figure 10. Duodenum, case 7. Tumor cells are focally positive for CK7. Figure 11. Duodenum, case 5. Focal nuclear immunoreactivity of β-catenin in tumor cells. Figure 12. Stomach, case 6. No p53 labeling is detected in tumor cells.

Mutation Analysis

Extracted genomic DNA from 4 (cases 1, 4, 6, and 8) and 5 (cases 1, 3, 4, 6, and 8) out of the 8 cases were successfully amplified with the primers for KRAS and GNAS, respectively; DNA of sufficient quality for analysis was not obtained from the other cases. The DNA sequencing analysis identified no KRAS or GNAS mutations, including KRAS codons 12 and 13 and GNAS codons 775 and 801, in any examined case.

Discussion

In the present study, pyloric and duodenal adenomas developed in elderly cats with a mean age of 10 years, which is consistent with previous findings.^6,18 No sex or breed predisposition was observed. Similar to previous studies, anorexia and vomiting frequently occurred.^6,18 In the present study, these clinical signs improved after polyp resection in 6/7 cases; therefore, anorexia and vomiting appear to be associated with pyloric and duodenal adenomas in cats. However, improvement of clinical signs was not observed in case 4, and intestinal lymphoma likely contributed to the signs in this case. Given the match of location, age and clinical signs, feline pyloric, and duodenal adenoma is presumably the same condition as adenomatous polyp of the feline pylorus and duodenum previously reported.^6,18

The distributions of AB-PAS, PCS, CD10, CDX2, CK7, CK19, and CK20 in normal pyloric and duodenal tissue were similar to those reported in previous human and feline studies with minor variations.^{4,7,9,14,20,21,26

–30} In the present study, immunolabeling for CK19, which has been detected in intestinal submucosal gland in humans,²⁹ was not observed in intestinal submucosal gland in cats.

In humans, gastric- and intestinal-type tumors in the alimentary tract are characterized by the presence of neutral mucin or goblet/Paneth cells, respectively.¹⁶ Gastric-type adenomas have been further divided into foveolar-, pyloric gland-, and oxyntic gland-type adenoma based on histopathology, mucin production, and peptide profiles.⁸ In pyloric gland adenoma, the neoplastic cells have a ground-glass appearance and positive staining for PCS, similar to the of pyloric gland-type mucin that is generally produced by the pyloric gland, mucous neck cells, and intestinal submucosal gland.⁸ In the present study, the majority of tumor cells in feline pyloric and duodenal adenomas had ground-glass cytoplasm, and histochemical and immunohistochemical phenotypes were similar to those of mucous neck cells and cells of the pyloric gland. In humans, pyloric gland adenoma commonly develops in the stomach and duodenum.^2,3,34 The present results demonstrated that the location, histopathology, and histochemical and immunohistochemical profiles of feline pyloric and duodenal adenomas were similar to those of human pyloric gland adenoma, suggesting that feline pyloric and duodenal adenomas are the counterpart of human pyloric gland adenoma.

Immunolabeling for β-catenin is normally detected at the cell membrane, and nuclear β-catenin localization indicates the activation of Wnt/β-catenin signaling.¹⁷ The aberrant activation of Wnt/β-catenin signaling contributes to tumorigenesis in many organs,⁵ and the nuclear accumulation of β-catenin is frequently observed in human gastrointestinal tumors.^25,31 In the present study, weak nuclear accumulation of β-catenin was observed in 2/8 cases, which is a lower incidence than the incidence of 60% previously reported in feline colorectal tumors.³³ This result is consistent with human duodenal adenoma, in which nuclear β-catenin is less frequently detected in the gastric type than in the intestinal type.²⁴ Therefore, excessive Wnt/β-catenin signaling may not be involved in the pathogenesis of feline pyloric and duodenal adenomas, in contrast to duodenal/intestinal adenomas in humans.

Immunohistochemical staining for p53 is used as a surrogate for a mutational analysis of TP53, and the strong and diffuse immunostaining of p53 suggests TP53 gene mutations.²² The P53 protein has been detected in various feline cancers by immunohistochemistry; however, diffuse immunolabeling for p53 has rarely been observed in feline colorectal tumors.^23,33 In humans, a previous study showed that approximately 70% of pyloric gland adenomas were immunopositive for p53 and the incidence of p53 expression was higher in cases with transition to adenocarcinoma.³⁵ In accordance with previous findings on feline colorectal cancer, neoplastic cells in feline pyloric and duodenal adenoma were negative for p53 in the present study. This result suggests that a p53 malfunction does not play a critical role in the tumorigenesis of feline pyloric and duodenal adenomas, in contrast to humans.

The KRAS gene regulates many crucial cellular processes, such as cell proliferation, differentiation, and survival in response to extracellular stimuli through the Ras signaling pathway. KRAS mutations, particularly at codons 12 and 13, are frequently involved in human gastrointestinal tumors, including pyloric gland adenoma.^1,3,19,32,34 KRAS mutations at codon 13 have also been found in feline colorectal adenocarcinoma and are suspected to be involved in tumor development.³³ However, in the present study, there were no KRAS mutations at this region in the 4 examined cases, and its role to the pathogenesis of feline pyloric and duodenal adenomas was not supported.

The GNAS gene encodes the guanine nucleotide-binding protein G α-subunit, and its activating mutations have been detected in tumors of various organs in humans, such as the pancreas, pituitary gland, bone, and gastrointestinal tract.¹³ In the human gastrointestinal tract, GNAS mutations are specifically found in pyloric gland adenoma, but not in other types of tumors, and are considered to be characteristic of pyloric gland adenoma.^19,34 More than 90% of mutations in the human GNAS gene involve codons 844 and 870, which correspond to codons 201 and 227 in the isoform Gnas-1.³² Protein sequence alignment showed >99% similarity between the human GNAS isoform Gnas-1 and the feline GNAS isoform; therefore, mutational hotspots in the human GNAS gene are equivalent to codons 775 and 801 in the feline GNAS gene.³⁶ However, no GNAS mutations were detected in feline pyloric and duodenal adenomas in the present study. Based on the absence of detectable KRAS mutations in the examined cases, feline pyloric and duodenal adenoma appears to have a different molecular pathogenesis than that of pyloric gland adenoma in humans. However, the mechanisms underlying the tumorigenesis of feline pyloric and duodenal adenoma were not clarified in the present study.

In conclusion, the present study revealed the histological and immunohistochemical features of feline pyloric and duodenal adenoma. Tumor cells were characterized by eosinophilic, ground-glass cytoplasm and were histochemically and immunohistochemically similar to mucous neck cells or pyloric gland cells. The nuclear accumulation of β-catenin was limited, and p53 immunolabeling was not detected. Neither KRAS nor GNAS mutations were found. Feline pyloric and duodenal adenomas were histologically similar to human pyloric gland adenomas, whereas its molecular features were not. Further investigations are needed to elucidate the pathogenesis of feline pyloric and duodenal adenoma.

Footnotes

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this manuscript.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iDs

James K. Chambers

Kazuyuki Uchida

References

Arber

Shapira

Ratan

, et al. Activation of c-K-ras mutations in human gastrointestinal tumors. Gastroenterology. 2000;118(6):1045–1050.

Chen

Scudiere

Abraham

, et al. Pyloric gland adenoma: an entity distinct from gastric foveolar type adenoma. Am J Surg Pathol. 2009;33(2):186–193.

Chlumská

Waloschek

Mukenšnabl

, et al. Pyloric gland adenoma: a histologic, immunohistochemical and molecular genetic study of 23 cases. Cesk Patol. 2015;51(3):137–143.

Chu

Weiss

. Keratin expression in human tissues and neoplasms. Histopathology. 2002;40(5):403–439.

Clevers

Nusse

. Wnt/β-catenin signaling and disease. Cell. 2012;149(6):1192–1205.

Daure

Jania

Jennings

, et al. Ultrasonographic and clinicopathological features of pyloroduodenal adenomatous polyps in cats. J Feline Med Surg. 2017;19(2):141–145.

Espinosa de los Monteros

Fernandez

Millan

, et al. Coordinate expression of cytokeratins 7 and 20 in feline and canine carcinomas. Vet Pathol. 1999;36(3):179–190.

Fukuyama

Rugge

Washington

. Tumours of the stomach. In: WHO Classification of Tumours. Digestive System Tumours. 5th ed. International Agency for Research on Cancer; 2019:59–104.

Gad

A. A

histochemical study of human alimentary tract mucosubstances in health and disease. I. Normal and tumours. Br J Cancer. 1969;23(1):52–63.

10.

Graf

Grüntzig

Boo

, et al. Swiss Feline Cancer Registry 1965–2008: the influence of sex, breed and age on tumour types and tumour locations. J Comp Pathol. 2016;154(2):195–210.

11.

Hashimoto

Ogawa

Matsubara

, et al. Familial adenomatous polyposis-associated and sporadic pyloric gland adenomas of the upper gastrointestinal tract share common genetic features. Histopathology. 2015;67(5):689–698.

12.

Hida

Yamamoto

Hirahashi

, et al. Duodenal neoplasms of gastric phenotype: an immunohistochemical and genetic study with a practical approach to the classification. Am J Surg Pathol. 2017;41(3):343–353.

13.

Innamorati

Wilkie

Kantheti

, et al. The curious case of Gαs gain-of-function in neoplasia. BMC Cancer. 2018;18(1):293.

14.

Katsuyama

Spicer

. Histochemical differentiation of complex carbohydrates with variants of the concanavalin A-horseradish peroxidase method. J Histochem Cytochem. 1978;26(4):233–250.

15.

Klimstra

Nagtegaal

Rugge

, et al. Tumours of the small intestine and ampulla. In: WHO Classification of Tumours. Digestive System Tumours. 5th ed. International Agency for Research on Cancer; 2019:111–131.

16.

Lewin

Appleman

. Carcinoma of the stomach. In: Rosai

, ed. Tumors of the Esophagus and Stomach. 3rd Series, Fascicle 18. Armed Forces Institute of Pathology; 1996.

17.

Lustig

Behrens

. The Wnt signaling pathway and its role in tumor development. J Cancer Res Clin Oncol. 2003;129(4):199–221.

18.

MacDonald

Mullen

Moroff

. Adenomatous polyps of the duodenum in cats: 18 cases (1985–1990). J Am Vet Med Assoc. 1993;202(4):647–651.

19.

Matsubara

Sekine

Kushima

, et al. Frequent GNAS and KRAS mutations in pyloric gland adenoma of the stomach and duodenum. J Pathol. 2013;229(4):579–587.

20.

Moll

Zimbelmann

Goldschmidt

, et al. The human gene encoding cytokeratin 20 and its expression during fetal development and in gastrointestinal carcinomas. Differentiation. 1993;53(2):75–93.

21.

Moskaluk

Zhang

Powell

, et al. Cdx2 protein expression in normal and malignant human tissues: an immunohistochemical survey using tissue microarrays. Mod Pathol. 2003;16(9):913–919.

22.

Murnyak

Hortobagyi

. Immunohistochemical correlates of TP53 somatic mutations in cancer. Oncotarget. 2016;7(40):64910–64920.

23.

Nasir

Krasner

Argyle

, et al. Immunocytochemical analysis of the tumour suppressor protein (p53) in feline neoplasia. Cancer Lett. 2000;155(1):1–7.

24.

Niwa

Kuwano

Tomita

, et al. The different pathogeneses of sporadic adenoma and adenocarcinoma in non-ampullary lesions of the proximal and distal duodenum. Oncotarget. 2017;8(25):41078–41090.

25.

Ogasawara

Tsukamoto

Mizoshita

, et al. Mutations and nuclear accumulation of beta-catenin correlate with intestinal phenotypic expression in human gastric cancer. Histopathology. 2006;49(6):612–621.

26.

Sato

Itoh

Hinoda

, et al. Expression of CD10/neutral endopeptidase in normal and malignant tissues of the human stomach and colon. J Gastroenterol. 1996;31(1):12–17.

27.

Sheahan

Jervis

. Comparative histochemistry of gastrointestinal mucosubstances. Am J Anat. 1976;146(2):103–131.

28.

Shiroshita

Watanabe

Ajioka

, et al. Re-evaluation of mucin phenotypes of gastric minute well-differentiated-type adenocarcinomas using a series of HGM, MUC5AC, MUC6, M-GGMC, MUC2 and CD10 stains. Pathol Int. 2004;54(5):311–321.

29.

Sonoue

Suda

Nobukawa

, et al. Cytokeratin and mucin expression in region of duodenal papilla [in Japanese]. Tandou (J Jpn Biliary Assoc). 2005;19(4):440–443.

30.

Stasiak

Purkis

Leigh

, et al. Keratin 19: predicted amino acid sequence and broad tissue distribution suggest it evolved from keratinocyte keratins. J Invest Dermatol. 1989;92(5):707–716.

31.

Takayama

Shiozaki

Shibamoto

, et al. Beta-catenin expression in human cancers. Am J Pathol. 1996;148(1):39–46.

32.

Tate

Bamford

Jubb

, et al. COSMIC: the catalogue of somatic mutations in cancer. Nucleic Acids Res. 2019;47(D1):D941–D947.

33.

Uneyama

Chambers

Nakashima

, et al. Histological classification and immunohistochemical study of feline colorectal epithelial tumors. Vet Pathol. 2020;58(2):305–314. doi:10.1177/0300985820974279

34.

Vieth

Kushima

Borchard

, et al. Pyloric gland adenoma: a clinico-pathological analysis of 90 cases. Virchows Arch. 2003;442(4):317–321.

35.

Vieth

Kushima

Mukaisho

, et al. Immunohistochemical analysis of pyloric gland adenomas using a series of Mucin 2, Mucin 5AC, Mucin 6, CD10, Ki67 and p53. Virchows Arch. 2010;457(5):529–536.

36.

Yates

Achuthan

Akanni

, et al. Ensembl 2020. Nucleic Acids Res. 2020;48(D1):D682–D688.

Feline pyloric and duodenal adenoma: A histological and immunohistochemical study

Abstract

Keywords

Materials and Methods

Results

Clinical and Endoscopic Findings

Histopathology

Histochemistry and Immunohistochemistry

Mutation Analysis

Discussion

Footnotes

Declaration of Conflicting Interests

Funding

ORCID iDs

References